General research interest - methylation dysfunction or lack of methyl folate or other methyl donors could be an underlying causal factor of both histamine excess and dysautonomia - due to epigenetic changes caused by poor methylation function in the cell nucleus. Can you find research or hypothesis articles supporting that premise?
1 post
15 web pages
Here's a synthesis of the research and hypotheses that link methylation dysfunction, particularly with methyl folate or other methyl donors, to both histamine excess and dysautonomia through epigenetic changes:
Methylation and Histamine:
Methylation and Histamine Metabolism: Methylation is crucial for the metabolism of histamine. The enzyme histamine N-methyltransferase (HNMT) requires S-adenosylmethionine (SAMe), a methyl donor, to methylate histamine for its degradation. A deficiency in methylation capacity could lead to an accumulation of histamine.
MTHFR Mutations: Mutations in the MTHFR gene, which is involved in the production of methyl folate, have been associated with histamine intolerance. Methyl folate is essential for the synthesis of SAMe, thus linking methylation deficits to histamine issues.
Histamine Receptors and Methylation: There's research indicating that methylation influences the expression and function of histamine receptors, which could affect how the body responds to histamine.
Methylation and Dysautonomia:
Epigenetic Regulation of Autonomic Function: Dysautonomia can involve numerous symptoms stemming from the autonomic nervous system's dysfunction. Epigenetic mechanisms, including DNA methylation, regulate gene expression which might alter autonomic function:
Neurotransmitter Synthesis: Methylation is involved in the synthesis of neurotransmitters like serotonin, norepinephrine, and dopamine, which are crucial for autonomic regulation. Methylation deficits could lead to neurotransmitter imbalances, contributing to dysautonomia.
Methylation in Neurological Disorders: There are broader implications of methylation in neurological health, including the regulation of genes involved in neuronal function and plasticity, which could be dysregulated in autonomic disorders.
Epigenetic Changes:
Gene Expression: Methylation affects gene expression by adding methyl groups to DNA, which can silence or activate genes. Poor methylation could, therefore, lead to improper gene expression related to both histamine metabolism and autonomic control.
Histamine and Methylation Pathways: The pathways for histamine degradation and those involved in methylation share common intermediates or cofactors like SAMe, suggesting a direct link where methylation dysfunction could impact histamine levels.
Hypotheses and Studies:
Walsh Research: Dr. William Walsh and others have proposed models where methylation issues, particularly under or over-methylation, correlate with various mental health issues, which can include autonomic symptoms. While not directly focusing on dysautonomia, they highlight the impact of methylation on neurotransmitter levels, which are relevant to autonomic function.
Methylation in Chronic Fatigue Syndrome: Studies on conditions like Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), where dysautonomia is common, have pointed to methylation changes as part of the pathology, suggesting an epigenetic link.
General Hypotheses: There are hypotheses in the literature suggesting that epigenetic changes due to methylation dysfunction could be a root cause or contributing factor to various systemic disorders, including those with autonomic symptoms. However, direct causal links specifically for dysautonomia with histamine excess due to methylation issues are still speculative and require more research.
While this research paints a picture of interconnected pathways, more direct studies specifically linking methylation dysfunction to both histamine excess and dysautonomia via epigenetic changes are needed. The current literature offers a foundational hypothesis but calls for further targeted research. If you're interested in a deeper dive, I can suggest looking into recent reviews or experimental studies on these topics.
Is dysautonomia related to histamine excess or mast cell degranulation?
There is emerging research and clinical evidence suggesting a potential link between dysautonomia, histamine excess, and mast cell degranulation, particularly in the context of conditions like Mast Cell Activation Syndrome (MCAS) or histamine intolerance. Here's how these might be related:
Histamine Excess and Dysautonomia:
Symptoms Overlap: Both histamine excess and dysautonomia can present with overlapping symptoms such as palpitations, flushing, headache, dizziness, and gastrointestinal issues. These symptoms can be confusing, leading to diagnostic challenges.
Histamine's Physiological Effects: Histamine acts on various receptors (H1, H2, H3, H4) which are spread throughout the body, including the cardiovascular system. High levels of histamine can cause vasodilation, which might contribute to symptoms like low blood pressure or orthostatic intolerance, common in dysautonomia.
Neurotransmitter Role: Histamine also functions as a neurotransmitter in the central nervous system. An imbalance could theoretically affect autonomic regulation, potentially leading to or exacerbating dysautonomia.
Mast Cell Degranulation:
Mast Cell Activation: Mast cells, when activated, release numerous mediators including histamine, but also cytokines, leukotrienes, and prostaglandins. This can lead to systemic effects that mimic or worsen autonomic dysfunction.
Vasomotor Instability: Mast cell mediators can cause significant vasodilation or vasoconstriction, impacting blood pressure regulation.
Neuroinflammation: The inflammatory mediators from mast cells can cause neuroinflammation, which might disrupt autonomic function or nerve signaling.
MCAS and Dysautonomia: There's a noted association where individuals with MCAS often also have symptoms of dysautonomia. This might be due to both conditions being part of broader systemic disorders or because mast cell activation directly affects autonomic function.
Clinical Observations:
Case Studies and Anecdotal Evidence: Many patients with dysautonomia report relief from symptoms when treated for histamine excess or mast cell issues, suggesting a clinical link.
Therapeutic Approaches: Medications that stabilize mast cells or block histamine receptors (like H1 and H2 blockers) are sometimes used in dysautonomia management, particularly when symptoms suggest histamine involvement.
Research:
Mechanistic Studies: There's a need for more mechanistic studies to understand how mast cell activation or histamine excess directly impacts the autonomic nervous system. Current research is largely observational or based on case studies.
Genetic Factors: Some genetic predispositions might link both conditions, where certain mutations could predispose individuals to both mast cell issues and autonomic dysfunction.
Given this complexity, if you're exploring this connection for personal health reasons, consulting with specialists in both autonomic disorders and allergy/immunology could be beneficial. Would you like me to look for recent studies or clinical guidelines on this topic?
My initial question bumped into CoV, CoV, CoV, which muddies the water a bit.
Is dysautonomia related to loss of ACE2 receptor function? Or how might it be related?
Dysautonomia refers to a dysfunction of the autonomic nervous system, which controls functions like heart rate, blood pressure, digestion, and temperature regulation. The ACE2 (Angiotensin-Converting Enzyme 2) receptor is better known for its role in the renin-angiotensin system, which regulates blood pressure and fluid balance, and has been notably discussed in the context of SARS-CoV-2 infections since the virus uses this receptor to enter cells.
There isn't a direct, well-established link in medical literature between dysautonomia and loss of ACE2 receptor function. However, here's how they might be theoretically related:
Cardiovascular Regulation: Both dysautonomia and the renin-angiotensin system (including ACE2) play roles in cardiovascular regulation. Dysautonomia can lead to symptoms like orthostatic hypotension or tachycardia, which might be influenced by disruptions in systems that ACE2 is part of. If there's a significant reduction in ACE2 function, it could potentially alter how blood pressure is regulated, thus having an indirect effect on autonomic function.
Inflammation and Immune Response: The ACE2 receptor has anti-inflammatory effects. A dysfunction or loss of function could lead to increased inflammation, which might indirectly affect the autonomic nervous system. Chronic inflammation is known to disrupt neural function, potentially contributing to or exacerbating dysautonomia.
Viral Infections: Given that SARS-CoV-2 uses ACE2 to enter cells, infections might lead to both direct damage to tissues where ACE2 is expressed and systemic effects like inflammation, which could impact autonomic function. There have been reports of post-viral dysautonomia, where symptoms might arise or worsen after infections that potentially affect ACE2 function.
Hormonal and Electrolyte Balance: ACE2 influences the balance of angiotensin peptides which can affect vasoconstriction and sodium balance. Dysregulation could influence the autonomic control of these systems, although this link is speculative.
While these connections suggest possible pathways, they are largely theoretical or based on indirect associations:
Research: Direct research linking dysautonomia specifically to ACE2 function is sparse. Most studies would look at broader impacts like those from cardiovascular health or viral infections rather than pinpointing ACE2 loss of function.
Clinical Observation: In clinical settings, if patients with known dysautonomia also have conditions affecting ACE2 (like severe COVID-19), monitoring might reveal symptomatic changes, but this would be observational rather than conclusive evidence of causality.
If you're interested in the latest research or are looking for clinical implications, I can suggest searching for recent studies or reviews that might discuss any new findings on this topic. Would you like me to do that?
I would add a 5th item to this list of common problems- dysautonomia.
Yes, good call.
I would agree, related. Autoimmune/oxidative stress, lack of vitamin D and selenium, hyperinflammation side effect. One of my posts on hyperinflammation spiral progressing through fibromyalgia and autoimmune thyroiditis to liver injury - too much active vitamin A involvement. https://open.substack.com/pub/denutrients/p/birth-of-a-graphic-on-retinoid-toxicity?r=os7nw&utm_campaign=post&utm_medium=web&showWelcomeOnShare=false
Grok with 15 links on comorbidity seen between POTS and autoimmune thyroiditis https://x.com/i/grok/share/eHSluTWL2V7jFRShbwOTwld5P
General research interest - methylation dysfunction or lack of methyl folate or other methyl donors could be an underlying causal factor of both histamine excess and dysautonomia - due to epigenetic changes caused by poor methylation function in the cell nucleus. Can you find research or hypothesis articles supporting that premise?
1 post
15 web pages
Here's a synthesis of the research and hypotheses that link methylation dysfunction, particularly with methyl folate or other methyl donors, to both histamine excess and dysautonomia through epigenetic changes:
Methylation and Histamine:
Methylation and Histamine Metabolism: Methylation is crucial for the metabolism of histamine. The enzyme histamine N-methyltransferase (HNMT) requires S-adenosylmethionine (SAMe), a methyl donor, to methylate histamine for its degradation. A deficiency in methylation capacity could lead to an accumulation of histamine.
MTHFR Mutations: Mutations in the MTHFR gene, which is involved in the production of methyl folate, have been associated with histamine intolerance. Methyl folate is essential for the synthesis of SAMe, thus linking methylation deficits to histamine issues.
Histamine Receptors and Methylation: There's research indicating that methylation influences the expression and function of histamine receptors, which could affect how the body responds to histamine.
Methylation and Dysautonomia:
Epigenetic Regulation of Autonomic Function: Dysautonomia can involve numerous symptoms stemming from the autonomic nervous system's dysfunction. Epigenetic mechanisms, including DNA methylation, regulate gene expression which might alter autonomic function:
Neurotransmitter Synthesis: Methylation is involved in the synthesis of neurotransmitters like serotonin, norepinephrine, and dopamine, which are crucial for autonomic regulation. Methylation deficits could lead to neurotransmitter imbalances, contributing to dysautonomia.
Methylation in Neurological Disorders: There are broader implications of methylation in neurological health, including the regulation of genes involved in neuronal function and plasticity, which could be dysregulated in autonomic disorders.
Epigenetic Changes:
Gene Expression: Methylation affects gene expression by adding methyl groups to DNA, which can silence or activate genes. Poor methylation could, therefore, lead to improper gene expression related to both histamine metabolism and autonomic control.
Histamine and Methylation Pathways: The pathways for histamine degradation and those involved in methylation share common intermediates or cofactors like SAMe, suggesting a direct link where methylation dysfunction could impact histamine levels.
Hypotheses and Studies:
Walsh Research: Dr. William Walsh and others have proposed models where methylation issues, particularly under or over-methylation, correlate with various mental health issues, which can include autonomic symptoms. While not directly focusing on dysautonomia, they highlight the impact of methylation on neurotransmitter levels, which are relevant to autonomic function.
Methylation in Chronic Fatigue Syndrome: Studies on conditions like Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), where dysautonomia is common, have pointed to methylation changes as part of the pathology, suggesting an epigenetic link.
General Hypotheses: There are hypotheses in the literature suggesting that epigenetic changes due to methylation dysfunction could be a root cause or contributing factor to various systemic disorders, including those with autonomic symptoms. However, direct causal links specifically for dysautonomia with histamine excess due to methylation issues are still speculative and require more research.
While this research paints a picture of interconnected pathways, more direct studies specifically linking methylation dysfunction to both histamine excess and dysautonomia via epigenetic changes are needed. The current literature offers a foundational hypothesis but calls for further targeted research. If you're interested in a deeper dive, I can suggest looking into recent reviews or experimental studies on these topics.
15 webpage links are at the Grok summary https://x.com/i/grok/share/SWPs5KtJYFW4sMKf8MorUx2mm
That was my refinement of this question:
https://x.com/i/grok/share/PPE8LclOg8LAy64owcFl4XlTF
Is dysautonomia related to histamine excess or mast cell degranulation?
There is emerging research and clinical evidence suggesting a potential link between dysautonomia, histamine excess, and mast cell degranulation, particularly in the context of conditions like Mast Cell Activation Syndrome (MCAS) or histamine intolerance. Here's how these might be related:
Histamine Excess and Dysautonomia:
Symptoms Overlap: Both histamine excess and dysautonomia can present with overlapping symptoms such as palpitations, flushing, headache, dizziness, and gastrointestinal issues. These symptoms can be confusing, leading to diagnostic challenges.
Histamine's Physiological Effects: Histamine acts on various receptors (H1, H2, H3, H4) which are spread throughout the body, including the cardiovascular system. High levels of histamine can cause vasodilation, which might contribute to symptoms like low blood pressure or orthostatic intolerance, common in dysautonomia.
Neurotransmitter Role: Histamine also functions as a neurotransmitter in the central nervous system. An imbalance could theoretically affect autonomic regulation, potentially leading to or exacerbating dysautonomia.
Mast Cell Degranulation:
Mast Cell Activation: Mast cells, when activated, release numerous mediators including histamine, but also cytokines, leukotrienes, and prostaglandins. This can lead to systemic effects that mimic or worsen autonomic dysfunction.
Vasomotor Instability: Mast cell mediators can cause significant vasodilation or vasoconstriction, impacting blood pressure regulation.
Neuroinflammation: The inflammatory mediators from mast cells can cause neuroinflammation, which might disrupt autonomic function or nerve signaling.
MCAS and Dysautonomia: There's a noted association where individuals with MCAS often also have symptoms of dysautonomia. This might be due to both conditions being part of broader systemic disorders or because mast cell activation directly affects autonomic function.
Clinical Observations:
Case Studies and Anecdotal Evidence: Many patients with dysautonomia report relief from symptoms when treated for histamine excess or mast cell issues, suggesting a clinical link.
Therapeutic Approaches: Medications that stabilize mast cells or block histamine receptors (like H1 and H2 blockers) are sometimes used in dysautonomia management, particularly when symptoms suggest histamine involvement.
Research:
Mechanistic Studies: There's a need for more mechanistic studies to understand how mast cell activation or histamine excess directly impacts the autonomic nervous system. Current research is largely observational or based on case studies.
Genetic Factors: Some genetic predispositions might link both conditions, where certain mutations could predispose individuals to both mast cell issues and autonomic dysfunction.
Given this complexity, if you're exploring this connection for personal health reasons, consulting with specialists in both autonomic disorders and allergy/immunology could be beneficial. Would you like me to look for recent studies or clinical guidelines on this topic?
My initial question bumped into CoV, CoV, CoV, which muddies the water a bit.
Is dysautonomia related to loss of ACE2 receptor function? Or how might it be related?
Dysautonomia refers to a dysfunction of the autonomic nervous system, which controls functions like heart rate, blood pressure, digestion, and temperature regulation. The ACE2 (Angiotensin-Converting Enzyme 2) receptor is better known for its role in the renin-angiotensin system, which regulates blood pressure and fluid balance, and has been notably discussed in the context of SARS-CoV-2 infections since the virus uses this receptor to enter cells.
There isn't a direct, well-established link in medical literature between dysautonomia and loss of ACE2 receptor function. However, here's how they might be theoretically related:
Cardiovascular Regulation: Both dysautonomia and the renin-angiotensin system (including ACE2) play roles in cardiovascular regulation. Dysautonomia can lead to symptoms like orthostatic hypotension or tachycardia, which might be influenced by disruptions in systems that ACE2 is part of. If there's a significant reduction in ACE2 function, it could potentially alter how blood pressure is regulated, thus having an indirect effect on autonomic function.
Inflammation and Immune Response: The ACE2 receptor has anti-inflammatory effects. A dysfunction or loss of function could lead to increased inflammation, which might indirectly affect the autonomic nervous system. Chronic inflammation is known to disrupt neural function, potentially contributing to or exacerbating dysautonomia.
Viral Infections: Given that SARS-CoV-2 uses ACE2 to enter cells, infections might lead to both direct damage to tissues where ACE2 is expressed and systemic effects like inflammation, which could impact autonomic function. There have been reports of post-viral dysautonomia, where symptoms might arise or worsen after infections that potentially affect ACE2 function.
Hormonal and Electrolyte Balance: ACE2 influences the balance of angiotensin peptides which can affect vasoconstriction and sodium balance. Dysregulation could influence the autonomic control of these systems, although this link is speculative.
While these connections suggest possible pathways, they are largely theoretical or based on indirect associations:
Research: Direct research linking dysautonomia specifically to ACE2 function is sparse. Most studies would look at broader impacts like those from cardiovascular health or viral infections rather than pinpointing ACE2 loss of function.
Clinical Observation: In clinical settings, if patients with known dysautonomia also have conditions affecting ACE2 (like severe COVID-19), monitoring might reveal symptomatic changes, but this would be observational rather than conclusive evidence of causality.
If you're interested in the latest research or are looking for clinical implications, I can suggest searching for recent studies or reviews that might discuss any new findings on this topic. Would you like me to do that?
https://x.com/i/grok/share/r7a8iORVIlxte4XKsF5NYaIqC
*ACE2 receptor dysfunction has weird ripple effects throughout the body and is likely related to methylation changes or gut dysbiosis too.