Mast Cells / Histamine: Friend or Foe!?

Mast Cells

Mast cells are immune cells that reside in virtually all body tissues that have a blood supply. Upon activation by diverse mechanisms (allergy reactions, microbe exposures, environmental exposures, immune initiated reactions), mast cells can secrete a broad variety of biologically active products that either are stored in the interior granules of cells (e.g., histamine, heparin, various proteases) or are produced on demand upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). These products are normal responses to mast cell activity. However, prolonged secretion due to chronic mast cell overload can cause destructive damage to cells, tissues and organs. There is evidence that prolonged mast cell activation and chronic inflammation are involved in tumor development and cancer.

Mast cells are best known for their functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. As you can see, outlined by the figure below, mast cells are involved in multiple responses of the body that are both defensive and harmful. There are many products that are excreted and secreted resulting from mast cell activation. It is important to know that mast cell activation is a normal response of defense and protection. Though when faulty, a plethora of unfavorable immune responses can result.

masscell

Mast Cells: the “Good” and the “Bad”

Mast cells are long-lived secretory cells derived from the bone marrow that are ordinarily found only in small numbers in the blood but that complete their differentiation and maturation in the micro environments of almost all vascularized tissues. Mast cells can proliferate after appropriate stimulation. Mature mast cells are abundant in tissues and organs exposed to the external environment, such as the skin, the lung, and the gut, and are often located close to potential targets of their mediators, such as skin, mucosal surfaces (gut and lung), glands, smooth muscle cells, vessels, lymph glands, nerves, etc. There are many health conditions that involve mast cell secretion and can cause significant disease burden and progression if not identified and remedied.

Mast Cell Initiated Conditions:

  • Allergic Asthma
  • Allergy and Hypersensitivity Reactions
  • Anaphylactic Shock
  • Autism
  • Autoimmune Disease
  • Bowel Inflammation (Celiac Disease, SIBO, LIBO, Ulcerative Colitis and Crohn’s Disease)
  • Brain Inflammation
  • Breast Cancer
  • Chronic Fatigue / FMS / SLE
  • Chronic Inflammation
  • Colon Cancer
  • Diabetes and Obesity
  • Dysautonomia
  • Ehlers-Danlos Syndromes
  • Genetic Susceptibility
  • Heart Failure, Cardiovascular Disease and Stroke
  • Hives (Urticaria)
  • Hormone and Neuro-hormone Regulation
  • Mast Cell Activation Syndrome
  • Mixed Organic Brain Syndrome
  • Multiple Myeloma
  • Multiple Sclerosis
  • Neurodegenerative Disease (Parkinson’s, Alzheimer’s Disease, Dementia, etc)
  • Neuroinflammation
  • POTS
  • Variety of Cancers

 

Mast Cells, Histamine and Methylation

I have discussed histamine and methylation in a previous blog. Histamine is an organic nitrogenous compound involved in immune responses, physiological functions in the gut, lungs and various tissues of the body. Also, it acts as a neurotransmitter involved in healthy neuro-adaptive function and methylation controls. In addition, histamine is involved in the inflammatory response.  See link for further information on histamine and methylation.

https://www.healthcoach7.com//histamine-methylation/

 

Mast Cells and Genetics

There are approximately 891 genes involved in mast cell activity generally with specific programming functions.               http://www.genecards.org/index.php?path=/Search/keyword/mast%20cells/0/20

The gene symbols are separated by a small space KIT KITLG CMA1, etc.

When using the link above you may need to sign in as a public user on Genecards. Copy/Paste in URL bar if needed.

 

Table 1:

KIT KITLG CMA1 CLNK KLRG1 C19orf59 MILR1 IL9 IL3 BTK CPA3 TPSAB1 TPSB2 TPSG1 FCER1A TPSD1 HRH4 CDKN2A HRH2 IL2 MPO TET2 KDR RASGRP4 ADORA3 MITF MMP10 ADORA2B HRH1 DHX15 NTRK3 LCP2 TLR3 TLR2 TLR4 TLR7 TLR1 TLR6 CCL2 TSTA3 GCNT2 MS4A2 ENPP3 HRH3 C5AR1 LYN IL33 LTB4R LTB4R2 C3 CCL5 CCL3 GCNT4 SNHG12 TPH1 GCNT1 FBXO21 EIF2B5 FIP1L1 EIF2B1 FBXO31 SH3KBP1 EIF2B2 PSTPIP2 EIF2B4 EIF2B3 NDST3 SPG21 SCRN1 HPGDS TMPRSS11D MYO1G SRGN TPSP2 TPSP1 ECSCR CD34 MIR142 PRSS29P IL31 CTRL NANOG IL4 IGKV2D-29 F2RL1 LAT2 C6orf25 HDC MIR143 SPN PECAM1 IGHE CD300LF TSLP IL13 S100A12 IL5 RARRES2 MIR132 CD52 DYT10 DEFB4A VCAM1 CTSG IL17A GATA2 CAMP IL8 NGF TAL1 GZMB SELE PTPRC ICAM1 CCL11 RNASE3 VAMP8 VTN SERPINB3 CASP3 ANPEP IFNG KLK11 ICAM3 ANXA5 MIR221 LAT GATA1 SERPINB4 MIR222 CD69 IFNL1 CD300A FOXF1 CLEC11A CD33 VIP CSF2 BCL6 KLRAP1 SYCN MCAM CCL4 CXCR3 LILRB2 SIGLEC7 TNFSF10 MIR146A AZU1 CDH5 LILRB4 HAVCR2 FCER1G SYK GZMK NR4A2 PCNA KCNN4 NTF4 CD44 PRG2 BCL2A1 IL10 LAIR1 MRGPRX2 FGF2 MAPK8 CXCL12 IL6 USF2 FCGR1A CDKN3 ACTC1 CXCL10 LTC4S TNF CD72 SNAP23 IL1RL1 TGFB1 IGK LGALS1 IL3RA CCR1 CDK20 C3AR1 INPP5D CD160 DEFB103B GJA1 ITGB1 TNFRSF4 CCL1 TNFRSF8 MAPK1 CXCR4 PIK3CG CSF1 DOC2A FAS TNFSF4 BAX DUSP19 VEGFA IL15 HAS2 SIGLEC8 SPHK1 MMP2 MUC5AC CD68 ENDOG NPPC CD22 CD9 CCR4 PTGS2 S1PR1 RHOD LILRB1 HIF1A CSF3 PRSS8 NGFR GATA3 BST1 CCR7 IL11 CXCL1 CD244 BMP6 BTG2 OSM CCND1 NTS ADCY10 ANG TNFRSF9 DEFA5 KNG1 IFNA1 IL25 PTGER2 TNFSF8 IL1A FCGR2B IL1B GPR34 CD1A IL32 CCR3 CCNG2 GZMA PLAUR S1PR2 GAST TYMP LILRA2 EGF CD59 LGALS3 STAT6 PRTN3 MMP9 CD38 HBEGF SLPI HMOX1 AREG CD63 CD151 PTGER1 INHA MMP3 BCL2 IL2RA ADORA2A UCN ITGB7 SST LAMP3 ADCYAP1 PVR CCL19 ICOSLG ITGAL ISG20 CTNNB1 IFNB1 PPP2R4 EDN1 JUN DOK1 SELPLG SAA2 VAMP7 SIRPA CXCR1 ADM SERPINB9 CASP8 ITGAX TMEM256-PLSCR3 ZAP70 S100A13 MMP1 BMP4 MAPK14 UCN2 PF4 STAT5A NOTCH1 LILRB3 ITK PPARG XCL1 TP53 CCL20 CSF2RA THPO CXCR2 TAC1 ACP1 ENO2 SELL PI3 IL13RA2 SERPINE1 CAT TJP1 ALCAM BCL10 CD80 FES CGB5 AOC1 PARP1 CASP1 STAT3 USF1 DEFA1 IL24 IL22 CRH NEU1 VIM EPX HGF CEBPA CALCA CPA1 SPI1 NFKB1 CYSLTR1 CFLAR CCL8 NOX1 CD36 MME ENSG00000227746 ENSG00000228267 ENSG00000228454 ENSG00000236625 BATF ALOX5 ENPP2 IL18R1 CXCL5 CLEC7A CCL22 PTGER4 ITGB2 CYSLTR2 AHR CCND2 HCLS1 CD300C SCRN2 NOS2 FGR SLC9A3R1 TRPV6 CD40LG STX4 SERPINA3 NOS3 F2R SOD1 AKT1 CXCL9 ABCB1 AGER CXCL2 CTSC IL18 ACTA2 ITGA5 TIMP1 IL9R TNFSF11 FCER2 CISH FOS RARA DEFA3 RAB3D CCR5 PLCG1 SGCB CASP9 ANXA1 BCL2L11 GRAP2 ITGA3 PTGDR2 CADM1 ERBB2 PTPN6 INHBA SRC AMBP AR EPOR TKT CD200R1L FCGR3A EPO LSR PIK3CA ABCC1 F2RL3 COL8A2 ELANE EFHD2 CCR6 MAPK3 HSPG2 SERPINB6 CD47 IL16 KRT1 KLK7 PTEN ELN PVRL2 STXBP2 SPHK2 SPARCL1 IL13RA1 CD84 P2RX7 TPT1 TNFAIP6 LTA FGF7 FN1 EDNRA SCG3 SLA HAPLN1 IFNA2 LILRA1 ITGA4 PTPN7 NTRK1 SIGLEC1 UNC13D SHC1 SPINT2 PTAFR CCL24 PPBP COX5A RAC1 CX3CL1 F11R CCL7 DUSP1 PIK3CD ITGA6 CD200R1 P2RX4 VAMP3 GAB2 IAPP ITGAM CRTC2 ITGAV PRSS27 CLU KRIT1 CD48 C4B_2 ENSG00000206340 EDN3 CNR1 TGFB2 NOD2 LILRB5 PTK2 BMX F2RL2 FIGF EIF6 ADAM17 PATZ1 PTGS1 CLEC4E CTSL PTGDS SERPINB1 TSPAN4 PLK1 CD226 TRPV2 FCGR2A PDE4A HMGB1 ARF6 CCL17 JAK3 EIF4EBP1 ELOF1 NBPF14 FYN ACE2 RGS13 CX3CR1 ADPRH RARB RECK TGIF1 DAB2 CD79A PTPN3 SERPINB2 ALOX15 NPPA VEGFC NFKBIA RHOH CCR8 RAF1 PXN CHI3L1 HPGD LAMP1 NTF3 KARS LCP1 MAP2K1 HCK VEGFB CERK UCP2 NFATC2 SEZ6L2 TGFB3 JAK2 SIGLEC5 AGT MAPK10 IL10RA APAF1 IL4R RAC2 ST14 B4GALNT1 ESR1 RASGRP1 TRPV1 C5 GRAP CPA5 CD164 SLC30A4 PGR FCGR2C STAT1 LTF CTGF PDGFRA NPY COL8A1 VAMP2 PTH FCGR3B RNPC3 MTOR PTGDR AXL PRKCD PTK2B HAS1 NR4A1 TOLLIP NRP1 SCYL1 CTSB PPARD CNR2 GP1BA DCN MAST1 PLAT NOTCH2 PDGFA MPP3 ABCC2 MATK LIFR CDC42 EPRS ZFPM1 NR0B2 FLT1 SRD5A1 CREB1 BGN SLC18A2 VWF C4B MBL2 RELA LEP CCL13 SERPINA5 JAM2 SAA1 POMC PLA2G4A SH2B3 TMPRSS11A TNFRSF13B IL5RA SLC9A3R2 GRB2 TFPI HSP90AA1 PARK7 BDNF ATP2A3 IL1R1 RLN2 NFATC1 HRAS HBB NR4A3 PPARA PLG ADORA1 CBL STX3 GNRH1 LPAR3 MBP REN GPR55 HP STAT5B TEC ADRB2 APOA2 FGA INPPL1 VAV1 PIK3R1 HTRA1 RASA1 P2RY6 FAAH KLKB1 MCF2 NR1I2 RAB5A ALDH1A2 PTPN11 SCAMP2 NOS1 NDRG1 MASTL CHUK CD97 PIK3CB MAP3K1 TGFBR1 PLD2 SWAP70 CAMK2G NME4 NMUR1 MAP3K2 TRAF6 HGS PPA1 TBXA2R TXK FOXO3 IL1RN SYT5 GAPDH PPP1R15A RASA2 P2RX1 PTGIR PDPK1 TMSB4X LAMA5 CPLX2 NFAM1 ARRB2 RAB37 YKT6 ITGA2B LPAR1 LAMP2 NLRP3 PRKCB NCK1 TJP2 ELK1 CCRL2 RUNX1 PFN1 MMP8 PDK1 PLA2G2A MEF2C CREB3 APC DGKQ PTGER3 PLA2G6 MAPK7 HNMT IL18RAP SCRN3 MAP2K7 TACR1 WIPF1 IKBKB ENO1 ALB GSK3B PTPN13 GPLD1 UBASH3B STX6 CBLB SERPINC1 PKM PSMC6 CSF2RB NF1 PTPN12 ALDOA ITGB5 PAK1 HTN3 RDH11 PRKCQ CRHR2 FDFT1 CHIT1 LPAR5 APP NPPB MAPKAPK2 C4A SLC18A1 UBC RABEP1 YWHAZ PRKCA MDH2 TGFBR3 FER STX2 MYH9 PPAP2A COL17A1 IKBKG AGK EMR2 MOK RAB27A NTRK2 PI4KB ARF1 F9 DYNLL1 SAMSN1 CPO SKAP1 NDST2 UBE2D1 SYN2 LONP1 NCS1 PTPRE APOA1 ROCK1 PAK2 TMPRSS15 IL1RAP NFE2L1 RABGEF1 APOA4 SLC17A5 PLD1 NRAS PAG1 PLCG2 F13A1 CD55 MAP2K4 APOE F2 STX5 TOM1L1 LGR6 LAMA3 CLASP2 FYB EPHB2 PRKD1 CHST3 ARHGEF2 ACE TRPM7 KCNA6 MAPK12 LEPR ARRB1 NSF EPHA3 PLSCR1 SOS1 ABCB7 QDPR VAPB TACR3 SYT1 ZFYVE9 PLA2G1B OPRM1 PLA2R1 PRKCI MAP2K2 CPQ CETP STXBP1 SYT2 MAP3K3 MAP2K5 NDST1 PLA1A PIK3R2 CRHR1 PLTP PRKCH UNC13A PLCD1 MAST3 ADK RYR1 GNAI3 DNM3 RPS3 PLA2G5 MAST2 PCSK6 LYST CLASP1 TBXAS1 PLSCR4 UNC13B PLA2G2D SEC23B MCC CHST11 PLSCR3 RIN3 GYPC CACNA1C RERE PLSCR2 UNC13C FGF12 DMD MAST4

 

This next table of mast cell related genes are associated specifically with mastocytosis, chronic mast cell activation and histamine involvement. These genes are involved in process activation in mast cell activation.

 

Table 2:

KIT KITLG IFNA2 PDGFRB TPSAB1 SLC27A4 HDC CD2 IL2RA PDGFRA KLRG1 SRGN TET2 SLC18A2 STAT5A CD5 CHIC2 MS4A1 CTSG FCER2 TNFRSF8 ZNF185 FIP1L1 CD69 CMA1 IGHE ISM1 IL9 JAK2 SMPD1 IL13 MITF RARA VIT NTRK3 PSMC5 FGFR1 IL5 PSMC4 PIK3CA TPSB2 C6orf25 NTF4 RASGRP4 IL13RA2 PDCD1 ACTC1 ASXL1 ENPP3 IL5RA ITGAX OSM RNASE3 SLC18A1 IFNA1 CBL MPO DNMT3A PF4 BGLAP IL6R NTF3 RAC2 VIM CALCA F3 NGF NRAS NTRK1 PIK3CD STAT5B TKT BCL2L1 RUNX1 TGFA NTRK2 PIK3R1 STAT3 IL1B BCL2 IL6 HRH2 HRH4 HRH1 HRH3 DHX15 TPSAB1 HDC CMA1 HNMT AOC1 IL3 IL31 IGHE TPT1 FCER1A KITLG IL4 CTRL F2RL1 MS4A2 IL5 DEFB4A DYT10 KIT RNASE3 SRGN KNG1 IL8 VIP GAST S100A12 IL13 PRG2 NGF TSLP CCL11 ICAM1 VCAM1 CSF2 IFNG CAMP SELE DEFB103B IL2 PECAM1 CCL2 C5AR1 IL9 CTSG IL6 ADCY10 CCL5 ENSG00000227746 ENSG00000228267 ENSG00000228454 ENSG00000236625 CDH5 EPX NPPC CD160 NTF4 IL10 INPP5D CCL4 MUC5AC PTPRC TAC1 ANXA5 SYK CCL3 KCNN4 LYN CSF1 TNF ADCYAP1 CDKN3 LTC4S UCN2 SST PCNA CXCL10 IL11 SLPI CXCR3 C4B_2 ENSG00000206340 C3AR1 CCL1 SPHK1 STAT6 TGFB1 UCN IL1B OSM ADORA2A PTGER2 FCGR2B ADM CASP1 IL15 PF4 PPBP MAPK8 SELL ALOX5 PI3 MAPK1 NGFR RHOD EDN1 CXCL12 ADORA2B CXCR4 IFNA1 HSPG2 CD9 MMP3 NTS CYSLTR1 CYSLTR2 VEGFA CALCA CXCL1 PPP2R4 LAMP3 ADORA3 ITGB1 SELPLG TLR2 SLC18A2 CXCL9 CRH PIK3CG IL1A PTGS2 MMP9 MPO CCR3 BAX ENPP3 TJP1 MMP2 HBEGF IL18 MMP1 CCL22 HIF1A CTNNB1 IL16 PDE4A NEU1 MME JUN PTAFR CTSC BMP6 BTK FCER2 EDN3 HMOX1 EGF TPH1 THPO ADORA1 FOS CAT ITGB2 SGCB SOD1 PARP1 PTGER4 IL2RA TLR4 VIM CCL7 NOS2 IFNA2 MAPK14 PTGDS NMUR1 CCL24 HGF MAPK3 NOS3 CNR1 NPPA CCR5 F2RL2 EDNRA ANXA1 F2R ADPRH ITGAM STAT3 CD40LG CD36 PTPN6 SRC IAPP ADAM17 KRIT1 TIMP1 C4B COX5A PIK3CA ELN AKT1 NPY CD226 FCGR2A C5 FGF7 LTF TKT NOD2 PLCG1 PTGS1 PRKCD CASP9 ABCB1 IL4R UCP2 EPO CD79A CCL13 CAMK2G RAF1 FN1 ITGAV ALB ATP2A3 RAC1 TBXA2R NTF3 ADRB2 NR4A1 MAPK10 VEGFC PTK2 PLA2G4A DGKQ MAP2K1 VWF JAK2 DCN HGS FGA STAT1 INPPL1 PTK2B POMC PLAT HTN3 NLRP3 C4A C3 CREB1 RELA CBL BDNF NPPB PLA2G6 GAPDH TACR1 IL1RN NOS1 PRKCA PTGER3 PLA2G2A PRKCB YWHAZ GSK3B PLA1A ROCK1 CRHR1 CD55 CPQ ACE OPRM1 DNM3

 

Mast Cells and Epigenetic Signaling

Epigenetic intelligence is a powerful tool that can program favorable signaling to change bad patterns. When the immune system fails to reset vital functions including mast cell activation, it is essential to determine where the fault lies. Equilibrium and homeostasis are two words that describe what should occur. However, with chronic irritations, these cells provoke hypersensitivity and inflammatory reactions and without proper identification and remedy, mast cells cycling will continue to be a concern. It is essential to identify genetic sensitivities, antigen exposures, microbial and viral initiators, nutritional vulnerabilities, immune and inflammation profiling, systemic controls including circadian stress adaptation and hormonal and neuro-hormonal triggers. It is not a simple task. There needs to be great preliminary clinical detective work in order to identify the root causes of disturbance. Here is a great article that outlines some of these relationships: http://www.ncbi.nlm.nih.gov/pubmed/24622794. Epigenetic intelligence programming is essential to change faulty inputs that initiate unfavorable gene signals. MCAD / MCAS will create faulty signals that may have transgenerational consequences.

Difficulties in Detection of Mast Cells

It is extremely difficult to adequately identify the intensity of mast cell disturbance by clinical testing due to limitations. As mentioned above, there are very few mast cells found in the circulating blood as these cells translocate to localized areas out of the circulation. However, there are enzyme controls, genetic controls, immune controls, inflammation controls and their products that need to be included in analysis. I am going to outline some of the key tests that I believe will be somewhat useful in narrowing down this complex process.

 

Current Lab Testing Criteria

Manifestation in an organ other than skin and either one major and one minor criterion or three minor criteria:

Major criterion
Bone marrow or extracutaneous biopsy with multifocal, dense infiltration of mast cells (aggregates of >15 mast cells)
Minor criteria
Serum tryptase >20 ng/mL (not applicable in associated clonal hematologic nonmast cell-lineage disorder)
Bone marrow smear or extracutaneous tissue biopsy showing ≥25% of mast cells with atypical or spindle-shaped morphology
Evidence of CD2 or CD25 on mast cells in bone marrow, blood, or extracutaneous tissue
KIT D816V point mutation in bone marrow, blood, or extracutaneous tissue
Laboratory Testing
 Initial, nonspecific testing
·                CBC – may reveal eosinophilia on cell differential; cytopenias may occur
·                Liver function assays
Serum tryptase concentration
o        Tryptase concentration correlates with total mast-cell burden in systemic mastocytosis
§     Tryptase concentration >20 ng/mL at least twice on separate occasions should be further evaluated for SM
§     Up to 20% of patients with SM have normal tryptase concentrations (usually more indolent forms [Afrin, 2014])
o        Increased tryptase concentration may indicate any of the following mast cell activation disorders
1.              Anaphylaxis
2.              Asthma
3.              Urticaria
4.              Autoimmune Reactivity
5.              Inflammation
Serum and urine histamine concentrations
·                Histamine concentration may not be elevated
·                Increased concentration may indicate any of the following
1.              Anaphylaxis
2.              Carcinoid tumors, particularly of gastric origin
3.              Lymphoproliferative disorders
4.              Mast cell activation disorders
5.              Myeloproliferative neoplasms (MPN)
6.              Autoimmune Disorders
7.              Chronic Inflammation
 
Genetic Testing
·                KIT (D816V) gene mutation testing (bone marrow, blood, tissue)
·                23andMe complete genetic sensitivities
 
Histology
Skin or bone marrow biopsy (≥2 cm)
1.              Recommended when tryptase is >20 ng/mL or high clinical suspicion exists for mastocytosis (eg, urticaria pigmentosa) in the presence of normal tryptase level
2.              Definitive diagnosis (major criterion) when ≥15 mast cells (with ≥25% spindle shaped) in aggregate detected by immunohistochemistry tryptase staining
3.              Immunohistochemistry (IHC) – CD2, CD25, CD117 (c-Kit), and mast cell tryptase on mast cells
4.              Genetic testing – KIT D816V mutation found in >70% of patients with systemic mastocytosis 23andMe data for sensitivities
5.              Recommend testing on bone marrow
6.              Low yield with peripheral blood, which usually contains no mast cells (except in mast cell leukemia)
7.              Minor criteria include IHC-positive stains, KIT gene mutation, persistent elevation of tryptase, atypical or spindled appearance of ≥25% mast cells
Prognosis
Associated with worse prognosis
Elevated tryptase >200 ng/mL – dysmyelopoiesis (usually defined as >30% bone marrow mast cells)
Evidence of impaired organ function
·                Cytopenia – absolute neutrophil count <1,000/µL; hemoglobin <10 g/dL, platelets <100,000/µL
·                Hepatomegaly with ascites and impaired liver function
·                Splenomegaly
·                Malabsorption
·                Skeletal lesions – osteolysis, osteoporosis
·                Life-threatening organopathy
·                KIT D816V mutation – predicts mast cell disease will be unresponsive to TKI therapy
 
Differential Diagnosis (Other Conditions Associated)
·                Asthma
·                Atopic disorders
·                Chronic urticaria
·                Anaphylaxis
·                Carcinoid tumors
·                VIPoma
·                Autoimmune disorders
·                Chronic Inflammatory Disorders
·                Myelodysplastic syndrome/myeloproliferative neoplasms
·                Chronic eosinophilic leukemia

Corrections in Mast Cell Activation

MCAD / MCAS treatment is not an easy road and it may involve addressing several key areas at the same time. Usually individuals suffering with the disease have associated immune dysfunction and autoimmune and inflammatory disease. Some of the common symptoms associated with this are seen below:

List of Associated Symptoms:

Blurred vision
Changes in mental state, such as confusion, irritability, poor attention span and impaired memory
Chest pain
Diarrhea
Dizziness
Fainting (a sudden, temporary loss of consciousness)
Fatigue
General weakness
Headache
Hot flushing – described as a dry feeling of heat, rather than the sort of wet heat you experience when sweating
Joint pain
Lightheadedness
Loss of appetite
Low Blood Pressure (Hypotension)
Nausea
Palpitations (irregular heartbeat)
Shortness of breath
Sleep Disturbance and stress maladaptation
Stomach pain caused by peptic ulcers
Swelling of the liver, which can cause jaundice (yellowing of the skin and eyes) and make you feel lethargic
Swelling of the lymph nodes
Swelling of the spleen, which can cause abdominal (tummy) and shoulder pain
Urinary symptoms (needing to pass urine frequently, or pain when passing urine)
Weakness
Weight loss or Gain

 

If you are experiencing any of these symptoms it essential to be sure that you have thorough evaluation in order to determine the causes and begin to pursue methodical treatment. Functional / Integrative medicine will provide a comprehensive foundation for identifying and treating the problem from a empowering position. It is essential to determine genetic sensitivities in complex cases as seen above in conditions and symptoms listed.

 

Where do I start?

  1. Identification of the Root Cause may need to be prioritized
  2. Genetic Sensitivities and Susceptibility Complete Raw Data and Interpretation (23andMe and HealthCoach7)
  3. Immune Profiling (e.g. immunophenotyping of defense cells including mast cells)
  4. Antigenic Load and Immune Sensitivities (e.g. food, environmental, toxic exposures i.e. heavy metals)
  5. Inflammation Burden (e.g. antibody burden)
  6. Nutritional Deficiencies (e.g. Macro and micronutrients, antioxidant and prooxidant defense)
  7. Viral Exposures (e.g. CMV, EBV, etc)
  8. Microbial Exposures (e.g. bad bacteria, mold and fungal elements)
  9. Vector Microbe Exposures (e.g. Lyme’s Disease)
  10. Methylation Assessment
  11. Functional Testing of Immune System, Detoxification and Gut

 

All of the above can be accomplished by blood, plasma, saliva, urine, stool and body fluids.

 

Deciding to Treat!

As you can see, extensive homework in identification is needed before deciding to treat. Treatment may involve many systems being addressed simultaneously. Forming your team is essential to start with. Do not rush into things as this a complex process and shot gun approaches fail. One of my theories is create an 18-month plan and break it into 3-month increments. Every three months, evaluate progress and modification in treatment and with this model, improvement is experienced all along the way. No miracle drugs or fixes here. Conventional treatments are often toxic and immune debilitating. I am not recommending supplements or nutrients at this time, as this again would be guessing and not productive. Loading up on methylation supportive supplements, nutritional products or drugs without proper workup is inefficient, potentially economically oppressive and often leads to increased anxiety. We do not want the process or treatment to become an obstacle to cure, this is why it essential to methodical and prioritize. I have discussed the frustrations of many people that began to treat off of the advice of other people and social media recommendations that turned out disastrous.

All the above information is to provide guidance for you and not give you a “quick fix.” You must have cooperative professionals to assist you through this process in order to achieve your goals. If you have been experiencing frustration and no solution, it’s time for a change. The key to this is better close management through the process as it is a difficult one to navigate.

The things to do and not to do:

1.     Do not address methylation challenges without proper identification of root causes
2.     Do not load up on supplements that are not identified to be specific for your condition
3.     Do not rush into conventional treatment with drugs that may harm your immune system
4.     Social media is not the best place to receive your advice do your research and check in with the knowledgeable professionals that will work to get you better
5.     Discern false advertising there is a ton of it out there on supplements, herbs, drugs, equipment, etc
6.     When experiencing symptoms as mentioned in this blog it is always better to have an advocate with you!
7.     Be methodical and compliant, as it will take time to get better!

 

Dr. John’s Favorite Nutrients to help with Mast Cells and Histamine

Quercetin: stabalizes mast cell activity and decreases the inflammatory action they produce in the gut.

Quercetin can be found in Maxiflav

Curcumin and CoQ10: stabilize cell membranes and decreases the inflammatory consequences mast cells initiate.

Curcumin and CoQ10 can both be found in CoCurcumin

Diamine Oxidase (DAO): assists with histamine degradation in order to assist in minimizing excessive mast cell cell reactions.

DAO can be found in HistoPlex

 

 

 


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