Case Studies
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October 19, 2023

A Case Study of Unlocking the Gut-Brain Connection in Mast Cell Activation and Dysautonomia

Medically Reviewed by
Updated On
September 17, 2024

The intricate relationship between the gut and the brain is increasingly recognized as a vital component of overall health. Recent research has shed light on the connection between dysautonomia, mast cell activation, and the gut-brain axis, highlighting their impact on various physiological processes. Mast cells, immune cells abundant in the gut, play a crucial role in allergic reactions and inflammation. Dysregulated mast cell activation can not only contribute to allergy symptoms but it can also contribute to a dysregulated nervous system. Exploring root causes such as food sensitivities, allergies, infections, dysbiosis, and vagus nerve dysregulation can unlock new perspectives and potential strategies for managing these conditions and optimizing health.

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Presenting Complaints: Fainting, Dysautonomia, Hypervigilance 

Ben, a 53-year-old male, husband, dad of three boys, and successful entrepreneur, has been experiencing several distressing symptoms over the past six months. After having COVID-19, he reported persistent throat clearing and excessive mucus production. Additionally, Ben has been dealing with heart rate spikes with standing, fainting episodes, facial swelling, lightheadedness, blood pressure dysregulation, flushing, palpitations, and occasional bouts of nausea. These symptoms have significantly impacted his daily life, prompting him to seek medical attention.

He noticed that certain dietary factors, such as increased consumption of gluten and sugar, appeared to exacerbate his symptoms. Notably, Ben experienced a vasovagal response, leading to hospitalization for three days. He cannot understand why this is happening, as he reports that he never has been anxious in the past. 

Ben also reports that he often skips lunch, follows a low-protein diet, and snacks on pretzels and chocolate. Sleep-related concerns include waking up in the early morning with palpitations, snoring, and feeling unrested. He also complains of chronic congestion, and he expressed his fearfulness of his current state of health. Additionally, Ben was prescribed omeprazole for silent reflux. 

Initial Lab Work 

The following labs were run:

GI-MAP Stool Test

Ben's GI-MAP Results
Ben's GI-MAP Results

Additional Labs

Ben's Additional Initial Labs
Ben's Initial Additional Labs

Tilt Table (+) Postural Orthostatic Tachycardia

  • Normal passive HUTT with mild orthostatic increase in HR
  • Dramatic increase in HR with SL NTG (Sublingual nitroglycerin) challenge resolving in seconds on supine positioning c/w postural tachycardia.

Cardiovascular Examination 

A thorough evaluation revealed Paroxysmal Tachycardia.

Lab Analysis

Following a thorough functional medicine and conventional medicine evaluation, Ben has been diagnosed with three conditions: mast cell activation, Postural Orthostatic Tachycardia Syndrome (POTS), and Paroxysmal Supraventricular Tachycardia (PSVT). Mast cell activation involves the abnormal release of chemical substances from mast cells, leading to the aforementioned symptoms of facial swelling, flushing, palpitations, and gastrointestinal distress. POTS refers to a dysregulation of the autonomic nervous system that manifests as lightheadedness, blood pressure fluctuations, and fainting upon assuming an upright position. PSVT is a condition characterized by rapid heart rates originating from the upper chambers of the heart, resulting in palpitations, dizziness, and shortness of breath.

Elevated Tryptase Interpretation

Elevated levels of tryptase in blood tests are indicative of mastocytosis, as tryptase is a marker for mast cell activation. Increased tryptase levels suggest an abnormal proliferation and activation of mast cells, supporting the diagnosis of mastocytosis and the need for further evaluation and management of this condition.

Low Vitamin D Interpretation

Low levels of vitamin D have been associated with compromised immune health, and some studies have suggested a potential link between vitamin D deficiency and increased susceptibility to anxiety-related symptoms. (2)

H. pylori, Staphylococcus, and Streptococcus Interpretation

These are all commonly found in the gastrointestinal tract and have been identified as potential mast cell activators and contributors to increased histamine levels. (2,3,4) These pathogenic bacteria have the ability to stimulate mast cells, leading to the release of histamine and other inflammatory mediators. Elevated histamine levels can trigger a cascade of symptoms associated with mast cell activation, such as flushing, palpitations, and gastrointestinal distress.

Elevated Beta-Glucuronidase Interpretation

The stool test also revealed elevated levels of beta-glucuronidase, an enzyme associated with impaired gut barrier function. Increased beta-glucuronidase activity can lead to increased levels of circulating histamine.

Anti-gliadin Antibodies Interpretation 

Ben’s laboratory results showed the presence of gluten IgA antibodies, indicating an immune response to gluten consumption. Gluten sensitivity can contribute to gut and systemic inflammation and permeability, triggering mast cell activation and worsening symptoms.

Allergy Testing Interpretation

Allergy testing revealed allergies to cat and dog dander.

Interventions

The following interventions were implemented: 

Vagus Nerve Exercises 

Ben was instructed to incorporate vagus nerve exercises into his daily routine. These exercises, including the salamander, valsalva maneuver, and humming, aimed to stimulate the vagus nerve, which plays a crucial role in regulating autonomic nervous system function. 

Daily Lymph Drainage

Lymph drainage is vital for Ben as it plays a crucial role in maintaining a healthy immune system and removing toxins, waste products, and inflammatory molecules from the body. 

Xlear and Mutes

Mute nasal dilators and Xlear nasal spray are two products beneficial for Ben's nasal health, immune function, and airflow. Mute dilators gently expand the nostrils, improving breathing and potentially reducing snoring. Xlear spray moisturizes the nasal passages, removes allergens, and supports a healthy nasal environment. 

Modified Elimination Diet

Ben was advised to follow a modified elimination diet, excluding gluten and dairy products. This dietary modification aims to reduce inflammation, as gluten and dairy are known triggers for immune reactions and gut inflammation. 

This was combined with a low histamine diet due to the presence of Mastocytosis, as it helps reduce histamine intake from food sources and minimize the activation of mast cells, thereby alleviating symptoms. This transitioned to a nutrient repletion diet as symptoms continued to improve.

2 g Salt/day  

In order to manage his Postural Orthostatic Tachycardia Syndrome (POTS), Ben required additional salt intake to help increase blood volume and improve orthostatic tolerance. 

DAO (Diamine Oxidase) Supplementation

Ben was prescribed DAO supplementation early on in the protocol. DAO is an enzyme responsible for the breakdown of histamine in the gut. 

Supplements: 

  • 1st Phorm Microfactor is a premium nutritional supplement that combines essential nutrients, including vitamins, minerals, probiotics for gut health, omega-3 fatty acids for brain and cardiovascular support, and antioxidants for cellular protection. 
  • 1st Phorm Magnesium is a comprehensive magnesium supplement that includes multiple forms of magnesium to promote better sleep quality and support the proper functioning of the nervous system and cardiovascular health.
  • Ashwagandha, an adaptogenic herb, has been shown to modulate the HPA (hypothalamic-pituitary-adrenal) axis, helping to regulate the stress response system and promote a healthy balance of cortisol, the primary stress hormone.
  • Inositol was chosen due to its potential benefits in managing anxiety and dysautonomia. Inositol is involved in neurotransmitter signaling pathways and has been studied for its positive effects on mood disorders, including anxiety.
  • Vitamin D3 with K2 5000 IU Vitamin D is essential for immune health and has been associated with reduced anxiety levels, as it plays a crucial role in modulating immune responses and promoting the production of neurotransmitters involved in mood regulation, such as serotonin.
  • Stinging nettle has been studied for its potential antihistamine properties, which may help alleviate symptoms related to histamine release, such as seasonal allergies, itching, and hives. The plant contains compounds that can inhibit histamine receptors and reduce the release of histamine.
  • Quercetin is a natural plant compound that has been studied for its potential to inhibit the release of histamine and reduce allergic responses in the body. Vitamin C has been found to enhance bioavailability and overall absorption within the body.

Phase 1 Gut Healing: 

Biocidin: Specifically in its liposomal form, is often recommended for biofilm disruptions due to its broad-spectrum antimicrobial properties and ability to penetrate the protective layers of biofilms, helping to break them down and support the eradication of pathogenic microorganisms.

Pylori Plex (Mastic Gum): Mastic gum, a resin derived from the Pistacia lentiscus tree, was prescribed because of its antimicrobial properties to treat H Pylori. 

SBI Protect: SBI Protect is a bovine immunoglobulin supplement that helps strengthen the gut barrier and modulate immune responses in the gut. SBI Protect can reduce the translocation of antigens and help mitigate immune reactions that trigger mast cell activation.

Phase 2 Gut Healing: 

Betaine HCL with Pepsin (Hydrochloric Acid): Ben was recommended HCL supplementation after negative H Pylori testing and performing the test for low stomach acidity to support proper digestion and nutrient absorption. 

Candibactin AR and BR: Candibactin AR and BR are herbal formulations containing botanical extracts with antimicrobial properties. These supplements were recommended to target opportunistic bacteria and rebalance the gut microbiota, supporting gastrointestinal health and reducing symptoms associated with mast cell activation.

3-Month Follow-Up

Ben's Follow-Up Labs
*Note: Biopsy noted no evidence of H. Pylori
Ben's Follow Up Labs 2

Follow-Up Interpretation

Ben's health has significantly improved with the personalized treatment plan. He no longer experiences high heart rate episodes, thanks to improved cardiac function and autonomic nervous system regulation. Engaging in regular strength training in a supportive group environment has not only enhanced his physical strength but also provided social support. His H. Pylori has resolved, stress is effectively managed, and a well-balanced diet has stabilized his energy levels. With these positive changes, Ben now enjoys a fulfilling family life, fully present and engaged with his loved ones.  

[signup]

Summary 

The gut-brain connection provides a fascinating lens through which to understand the complex interplay between dysautonomia, mast cell activation, and optimal health. By identifying and treating underlying gut infections, restoring a healthy balance of gut bacteria, improving vagal tone, and addressing airway dysfunction and immune health, it is possible to alleviate symptoms, reduce mast cell activation, regulate the nervous system, and support overall healing. By embracing a holistic view and comprehensive approach that considers the intricate connections within our bodies, we can successfully manage mast cell activation and dysautonomia and forge a path toward greater health and vitality.

Learn More

Podcast Episode: Harnessing the Power of Mindset, Nutrition, and Movement with Dr. Arianne Missimer

The intricate relationship between the gut and the brain is increasingly recognized as a vital component of overall health. Recent research has shed light on the connection between dysautonomia, mast cell activation, and the gut-brain axis, highlighting their impact on various physiological processes. Mast cells, immune cells abundant in the gut, play a crucial role in allergic reactions and inflammation. Dysregulated mast cell activation can contribute to allergy symptoms and may also affect the nervous system. Exploring factors such as food sensitivities, allergies, infections, dysbiosis, and vagus nerve function can provide new perspectives and potential strategies for managing these conditions and supporting health.

[signup]

Presenting Complaints: Fainting, Dysautonomia, Hypervigilance 

Ben, a 53-year-old male, husband, dad of three boys, and successful entrepreneur, has been experiencing several distressing symptoms over the past six months. After having COVID-19, he reported persistent throat clearing and excessive mucus production. Additionally, Ben has been dealing with heart rate spikes with standing, fainting episodes, facial swelling, lightheadedness, blood pressure changes, flushing, palpitations, and occasional bouts of nausea. These symptoms have significantly impacted his daily life, prompting him to seek medical attention.

He noticed that certain dietary factors, such as increased consumption of gluten and sugar, appeared to exacerbate his symptoms. Notably, Ben experienced a vasovagal response, leading to hospitalization for three days. He cannot understand why this is happening, as he reports that he never has been anxious in the past. 

Ben also reports that he often skips lunch, follows a low-protein diet, and snacks on pretzels and chocolate. Sleep-related concerns include waking up in the early morning with palpitations, snoring, and feeling unrested. He also complains of chronic congestion, and he expressed his fearfulness of his current state of health. Additionally, Ben was prescribed omeprazole for silent reflux. 

Initial Lab Work 

The following labs were run:

GI-MAP Stool Test

Ben's GI-MAP Results
Ben's GI-MAP Results

Additional Labs

Ben's Additional Initial Labs
Ben's Initial Additional Labs

Tilt Table (+) Postural Orthostatic Tachycardia

  • Normal passive HUTT with mild orthostatic increase in HR
  • Dramatic increase in HR with SL NTG (Sublingual nitroglycerin) challenge resolving in seconds on supine positioning c/w postural tachycardia.

Cardiovascular Examination 

A thorough evaluation revealed Paroxysmal Tachycardia.

Lab Analysis

Following a thorough functional medicine and conventional medicine evaluation, Ben has been diagnosed with three conditions: mast cell activation, Postural Orthostatic Tachycardia Syndrome (POTS), and Paroxysmal Supraventricular Tachycardia (PSVT). Mast cell activation involves the abnormal release of chemical substances from mast cells, leading to the aforementioned symptoms of facial swelling, flushing, palpitations, and gastrointestinal distress. POTS refers to a dysregulation of the autonomic nervous system that manifests as lightheadedness, blood pressure fluctuations, and fainting upon assuming an upright position. PSVT is a condition characterized by rapid heart rates originating from the upper chambers of the heart, resulting in palpitations, dizziness, and shortness of breath.

Elevated Tryptase Interpretation

Elevated levels of tryptase in blood tests are indicative of mast cell activation. Increased tryptase levels suggest an abnormal proliferation and activation of mast cells, supporting the need for further evaluation and management of this condition.

Low Vitamin D Interpretation

Low levels of vitamin D have been associated with compromised immune health, and some studies have suggested a potential link between vitamin D deficiency and increased susceptibility to anxiety-related symptoms. (2)

H. pylori, Staphylococcus, and Streptococcus Interpretation

These are all commonly found in the gastrointestinal tract and have been identified as potential mast cell activators and contributors to increased histamine levels. (2,3,4) These bacteria may stimulate mast cells, leading to the release of histamine and other inflammatory mediators. Elevated histamine levels can trigger a cascade of symptoms associated with mast cell activation, such as flushing, palpitations, and gastrointestinal distress.

Elevated Beta-Glucuronidase Interpretation

The stool test also revealed elevated levels of beta-glucuronidase, an enzyme associated with gut barrier function. Increased beta-glucuronidase activity can lead to increased levels of circulating histamine.

Anti-gliadin Antibodies Interpretation 

Ben’s laboratory results showed the presence of gluten IgA antibodies, indicating an immune response to gluten consumption. Gluten sensitivity can contribute to gut and systemic inflammation and permeability, potentially triggering mast cell activation and worsening symptoms.

Allergy Testing Interpretation

Allergy testing revealed allergies to cat and dog dander.

Interventions

The following interventions were implemented: 

Vagus Nerve Exercises 

Ben was instructed to incorporate vagus nerve exercises into his daily routine. These exercises, including the salamander, valsalva maneuver, and humming, aimed to stimulate the vagus nerve, which plays a crucial role in regulating autonomic nervous system function. 

Daily Lymph Drainage

Lymph drainage is important for Ben as it plays a role in maintaining a healthy immune system and removing waste products from the body. 

Xlear and Mutes

Mute nasal dilators and Xlear nasal spray are two products that may support Ben's nasal health and airflow. Mute dilators gently expand the nostrils, potentially improving breathing. Xlear spray moisturizes the nasal passages and may help maintain a healthy nasal environment. 

Modified Elimination Diet

Ben was advised to follow a modified elimination diet, excluding gluten and dairy products. This dietary modification aims to reduce potential inflammation, as gluten and dairy can be triggers for immune reactions and gut inflammation. 

This was combined with a low histamine diet due to the presence of Mastocytosis, as it helps reduce histamine intake from food sources and minimize the activation of mast cells, thereby potentially alleviating symptoms. This transitioned to a nutrient repletion diet as symptoms continued to improve.

2 g Salt/day  

In order to manage his Postural Orthostatic Tachycardia Syndrome (POTS), Ben required additional salt intake to help support blood volume and improve orthostatic tolerance. 

DAO (Diamine Oxidase) Supplementation

Ben was prescribed DAO supplementation early on in the protocol. DAO is an enzyme that helps break down histamine in the gut. 

Supplements: 

  • 1st Phorm Microfactor is a nutritional supplement that combines essential nutrients, including vitamins, minerals, probiotics for gut health, omega-3 fatty acids for brain and cardiovascular support, and antioxidants for cellular protection. 
  • 1st Phorm Magnesium is a magnesium supplement that includes multiple forms of magnesium to support sleep quality and the proper functioning of the nervous system and cardiovascular health.
  • Ashwagandha, an adaptogenic herb, has been shown to modulate the HPA (hypothalamic-pituitary-adrenal) axis, helping to support the stress response system and promote a healthy balance of cortisol, the primary stress hormone.
  • Inositol was chosen due to its potential benefits in managing anxiety and dysautonomia. Inositol is involved in neurotransmitter signaling pathways and has been studied for its positive effects on mood disorders, including anxiety.
  • Vitamin D3 with K2 5000 IU Vitamin D is essential for immune health and has been associated with reduced anxiety levels, as it plays a role in modulating immune responses and promoting the production of neurotransmitters involved in mood regulation, such as serotonin.
  • Stinging nettle has been studied for its potential antihistamine properties, which may help alleviate symptoms related to histamine release, such as seasonal allergies, itching, and hives. The plant contains compounds that can inhibit histamine receptors and reduce the release of histamine.
  • Quercetin is a natural plant compound that has been studied for its potential to inhibit the release of histamine and reduce allergic responses in the body. Vitamin C has been found to enhance bioavailability and overall absorption within the body.

Phase 1 Gut Healing: 

Biocidin: Specifically in its liposomal form, is often recommended for biofilm disruptions due to its broad-spectrum antimicrobial properties and ability to penetrate the protective layers of biofilms, helping to break them down and support the management of pathogenic microorganisms.

Pylori Plex (Mastic Gum): Mastic gum, a resin derived from the Pistacia lentiscus tree, was prescribed because of its antimicrobial properties to help manage H Pylori. 

SBI Protect: SBI Protect is a bovine immunoglobulin supplement that helps strengthen the gut barrier and modulate immune responses in the gut. SBI Protect can reduce the translocation of antigens and help mitigate immune reactions that may trigger mast cell activation.

Phase 2 Gut Healing: 

Betaine HCL with Pepsin (Hydrochloric Acid): Ben was recommended HCL supplementation after negative H Pylori testing and performing the test for low stomach acidity to support proper digestion and nutrient absorption. 

Candibactin AR and BR: Candibactin AR and BR are herbal formulations containing botanical extracts with antimicrobial properties. These supplements were recommended to target opportunistic bacteria and support the balance of the gut microbiota, supporting gastrointestinal health and reducing symptoms associated with mast cell activation.

3-Month Follow-Up

Ben's Follow-Up Labs
*Note: Biopsy noted no evidence of H. Pylori
Ben's Follow Up Labs 2

Follow-Up Interpretation

Ben's health has significantly improved with the personalized treatment plan. He no longer experiences high heart rate episodes, thanks to improved cardiac function and autonomic nervous system regulation. Engaging in regular strength training in a supportive group environment has not only enhanced his physical strength but also provided social support. His H. Pylori has resolved, stress is effectively managed, and a well-balanced diet has stabilized his energy levels. With these positive changes, Ben now enjoys a fulfilling family life, fully present and engaged with his loved ones.  

[signup]

Summary 

The gut-brain connection provides a fascinating lens through which to understand the complex interplay between dysautonomia, mast cell activation, and optimal health. By identifying and addressing underlying gut infections, supporting a healthy balance of gut bacteria, improving vagal tone, and considering airway function and immune health, it is possible to support symptom management, reduce mast cell activation, and promote overall well-being. By embracing a holistic view and comprehensive approach that considers the intricate connections within our bodies, we can support the management of mast cell activation and dysautonomia and forge a path toward greater health and vitality.

Learn More

Podcast Episode: Harnessing the Power of Mindset, Nutrition, and Movement with Dr. Arianne Missimer

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.

Learn more

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Lab Tests in This Article

  1. Bhuiyan P, Chen Y, Karim M, Dong H, Qian Y. Bidirectional communication between mast cells and the gut-brain axis in neurodegenerative diseases: Avenues for therapeutic intervention. Brain Res Bull. 2021 Jul;172:61-78. https://doi.org/10.1016/j.brainresbull.2021.04.010. Epub 2021 Apr 20. PMID: 33892083.
  2. Akpınar, Ş., Karadağ, M.G. Is Vitamin D Important in Anxiety or Depression? What Is the Truth?. Curr Nutr Rep 11, 675–681 (2022). https://link.springer.com/article/10.1007/s13668-022-00441-0
  3. Lv, Yp., Teng, Ys., Mao, Fy. et al. Helicobacter pylori-induced IL-33 modulates mast cell responses, benefits bacterial growth, and contributes to gastritis. Cell Death Dis 9, 457 (2018). https://www.nature.com/articles/s41419-018-0493-1
  4. Rocha-de-Souza CM, Berent-Maoz B, Mankuta D, Moses AE, Levi-Schaffer F. Human mast cell activation by Staphylococcus aureus: interleukin-8 and tumor necrosis factor alpha release and the role of Toll-like receptor 2 and CD48 molecules. Infect Immun. 2008 Oct;76(10):4489-97.https://journals.asm.org/doi/10.1128/iai.00270-08 Epub 2008 Jul 21. PMID: 18644875; PMCID: PMC2546849.
  5. von Beek C, Waern I, Eriksson J, Melo FR, Robinson C, Waller AS, Sellin ME, Guss B, Pejler G. Streptococcal sagA activates a proinflammatory response in mast cells by a sublytic mechanism. Cell Microbiol. 2019 Sep;21(9):e13064.https://onlinelibrary.wiley.com/doi/10.1111/cmi.13064 Epub 2019 Jul 7. PMID: 31155820; PMCID: PMC6771685.
  6. Smith GD, Fry MM, Taylor D, Morgans A, Cantwell K. Effectiveness of the Valsalva Manoeuvre for reversion of supraventricular tachycardia. Cochrane Database Syst Rev. 2015 Feb 18;2015(2):CD009502. https://doi.org/10.1002/14651858.CD009502.pub3. PMID: 25922864; PMCID: PMC7104204.
  7. Gelardi M, Porro G, Sterlicchio B, Quaranta N, Ciprandi G, Group On Sonoring IS. Internal and external nasal dilatator in patients who snore: a comparison in clinical practice. Acta Biomed. 2019 Jan 11;90(2-S):10–4. https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/8096 PMID: 30715031; PMCID: PMC6502076.
  8. Concerto C, Chiarenza C, Di Francesco A, Natale A, Privitera I, Rodolico A, Trovato A, Aguglia A, Fisicaro F, Pennisi M, et al. Neurobiology and Applications of Inositol in Psychiatry: A Narrative Review. Current Issues in Molecular Biology. 2023; 45(2):1762-1778. https://www.mdpi.com/1467-3045/45/2/113
  9. Roschek B Jr, Fink RC, McMichael M, Alberte RS. Nettle extract (Urtica dioica) affects key receptors and enzymes associated with allergic rhinitis. Phytother Res. 2009 Jul;23(7):920-6. https://onlinelibrary.wiley.com/doi/10.1002/ptr.2763 PMID: 19140159.
  10. Jafarinia M, Sadat Hosseini M, Kasiri N, Fazel N, Fathi F, Ganjalikhani Hakemi M, Eskandari N. Quercetin with the potential effect on allergic diseases. Allergy Asthma Clin Immunol. 2020 May 14;16:36. https://aacijournal.biomedcentral.com/articles/10.1186/s13223-020-00434-0 PMID: 32467711; PMCID: PMC7227109.
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