Milk allergy – IgE mediated – Non-IgE mediated – Lactose Intolerance

ReverseFX – Milk Allergy –IgE mediated – Non IgE mediated – Lactose Intolerance

ReverseFX contains MCT powder (Medium-chain triglycerides).

By law, MCT powder is classified and grouped together with milk. MCTs are found in:

  • coconut oil
  • palm kernel oil
  • milk
  • butter

The MCT powder found in ReverseFX is derived from coconut.

But, what is a Milk Allergy?

Milk Allergy – IgE mediated – Non IgE mediated

Milk allergy is an adverse immune reaction to one or more proteins in cow’s milk. In the United States, 90% of allergic responses to foods are caused by eight foods, with cow’s milk being the most common.

One function of the immune system is to defend against infections by recognizing foreign proteins, but it should not over-react to food proteins.

In people with rapid reactions (IgE-mediated milk allergy), the dose capable of provoking an allergic response can be as low as a few milligrams.

See Food Allergies – IgE-mediated post here:

https://www.facebook.com/groups/442113449949864/?post_id=656723878488819

B cells, a subset of white blood cells, rapidly synthesize and secrete immunoglobulin E (IgE), a class of antibody which bind to antigens, i.e., the foreign proteins. Thus, immediate reactions are described as IgE-mediated.

The delayed reactions involve non-IgE-mediated immune mechanisms initiated by B cells, T cells, and other white blood cells.

For milk allergy, non-IgE-mediated responses are more common than IgE-mediated.

Non-IgE-mediated responses are classified as Enterocolitis disease, which we will touch on later in this post.

Conditions caused by food allergies are classified into three groups according to the mechanism of the allergic response:

  • IgE-mediated (classic) – the most common type, manifesting as acute changes that occur shortly after eating, and may progress to anaphylaxis
  • Non-IgE mediated – characterized by an immune response not involving IgE; may occur hours to days after eating, complicating the diagnosis
  • IgE- and non-IgE-mediated – a hybrid of the above two types

Allergic reactions are hyperactive responses of the immune system to generally innocuous substances, such as proteins in the foods we eat. Some proteins trigger allergic reactions while others do not.

Milk Allergy, also known as milk allergic reaction, is related to goat milk allergy and lactose intolerance. An important gene associated with Milk Allergy is CSN1S1 (Casein Alpha S1), and among its related pathways/superpathways are Innate Immune System and ERK Signaling.

CSN1S1 (Casein Alpha S1) has an important role in the capacity of milk to transport calcium phosphate.

CSN1S1 (Casein Alpha S1) also directly cross talks with bradykinin B1 receptors.

Bradykinin is generated in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy.

Receptor binding of Bradykinin leads to an increase in the cytosolic calcium ion concentration, ultimately resulting in chronic and acute inflammatory responses.

Resveratrol suppresses Bradykinin inflammatory responses.

CSN1S1 (Casein Alpha S1) is regulated by CSNK2A1 Gene – Casein Kinase 2 Alpha 1.

Therefore, if we modulate Casein Kinase 2 we can impact the function of CSN1S1, which is the #1 gene associated with Milk Allergy.

Casein Kinase 2 is a “hot spot” in the 20,000+ genes we possess. It intersects with many of the top controlling genes in our entire genetic makeup.

It regulates numerous cellular processes, such as cell cycle progression, apoptosis, and transcription, as well as viral infection.

It phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB.

During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV.

It plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at ‘Ser-90’ which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621).

Compounds for CSNK2A1 Gene – From: DrugBank, ApexBio, DGIdb, HMDB, Tocris, and Novoseek:

  • Resveratrol
  • Quercetin (found in Prunella Vulgaris/Self Heal)
  • Ellagic acid (found in Pomegranate extract)
  • Emodin (found in Sea Buckthorn)

Compounds for Milk Allergy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

  • Vitamin C (found in various ingredients in ReverseFX, specifically Sea Buckthorn)
  • Tannic acid – found in several compounds in ReverseFX (Pomegranate extract, Prunella vulgaris (Self-heal), Dan Shen Sea Buckthorn, Baical skullcap, Ashwaganda, Ginger root, Kudzu root)
  • Vitamin K2 (found in various ingredients in ReverseFX, specifically Nattokinase and Self Heal)
  • Calcium (found in various ingredients in ReverseFX, specifically Shilajit)
  • Soy Bean (found in Nattokinase and Kudzu root, which Kudzu contains isoflavones, including puerarin (about 60% of the total isoflavones), daidzein, daidzin (structurally related to genistein)

Non-IgE Mediated Immune Responses

Allergic Hypersensitivity Disease and Enterocolitis are two of the top Non IgE Mediated clinical manifestations of allergies (milk).

Enterocolitis

Enterocolitis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon.

It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes, such as Non IgE Mediated Immune Responses.

An important gene associated with Enterocolitis is NLRC4 (NLR Family CARD Domain Containing 4), and among its related pathways/superpathways are Innate Immune System and Shigellosis.

NLRC4 is a member of the caspase recruitment domain-containing NLR family. Family members play essential roles in innate immune response to a wide range of pathogenic organisms, tissue damage and other cellular stresses. Mutations in this gene result in autoinflammation with infantile enterocolitis.

NLRC4 is a key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis (PubMed:15107016). The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria (By similarity).

NLRC4 requires Inhibitors of apoptosis, through the BIRC7 Gene. The BIR domain is essential for inhibitory activity and interacts with caspases. Its anti-apoptotic activity of BIRC7 is mediated through the inhibition of CASP3, CASP7, and CASP9, as well as by its E3 ubiquitin-protein ligase activity. BIRC7 has the ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival. BIRC7 protects against apoptosis induced by TNF or by chemical agents.

Bcl-2 (B-cell lymphoma 2) regulates proteins that regulate cell death (apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosis. Intrinsic apoptosis is controlled by the BCL-2 family of proteins.

Auto-immune

Apoptosis plays an active role in regulating the immune system. When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. In the case of defective apoptosis, it may contribute to the etiological aspects of autoimmune diseases.

BCL2 (BCL2 Apoptosis Regulator) regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).

Modulating BCL-2, in turn, regulates the function of BIRC7, and subsequently impacts the NLRC4 inflammasome, thus supporting the body against Enterocolitis and Non IgE Mediated Immune Responses.

  • BCL-2 Modulators:
  • Luteolin (strongest) – found in Prunella Vulgaris (Self heal)
  • Resveratrol
  • Genistein – found in Nattokinase and structurally similar compounds found in Kudzu root.
  • Vinpocetine – through TNF-α and PDE inhibition
  • Withaferin-A/Ashwagandha
  • MCT/Coconut
  • Beta glucans
  • Quercetin – found in Prunella Vulgaris (Self-heal)

Furthermore, the TAB1 Gene, MAPK12, and MAPK13 genes also assist in regulating the aforementioned. Supporting these genes and their pathways will help ensure optimal functioning capacity.

TAB1 – requires Manganese (found in Shilajit)

MAPK12/13 – requires Magnesium (found in Shilajit). These also require P38 MAP kinase inhibitors.

P38 MAP kinase inhibitors:

  • Prunella Vulgaris (Self-heal) contains proanthocyanidins, a class of naturally occurring flavonoids, inhibit ER stress-induced p38 activation cascades.
  • Kudzu root
  • Tanshinone IIA – found in Dan Shen
  • Ginger root

Licorice modulates Caspase 3, the executioner of apoptosis, which also communicates with BCL-2.

Compounds for Enterocolitis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

  • Zinc – found in Shilajit and several other compounds in ReverseFX
  • Coconut – MCT oil
  • Vitamin E – found in several compounds in ReverseFX, specifically Sea Buckthorn
  • Soy Bean – found in Nattokinase and Kudzu root, which Kudzu contains isoflavones, including puerarin (about 60% of the total isoflavones), daidzein, daidzin (structurally related to genistein)
  • Vitamin A – found in several compounds in ReverseFX
  • Vitamin C – found in several compounds in ReverseFX
  • Omega 3 Fatty Acid – found in Sea Buckthorn
  • Tannic acid – found in several compounds in ReverseFX (Pomegranate extract, Prunella vulgaris (Self-heal), Dan Shen Sea Buckthorn, Baical skullcap, Ashwaganda, Ginger root, Kudzu root)
  • Copper – found in Shilajit
  • Chromium – found in Shilajit
  • Silicon – found in Shilajit
  • Manganese – found in Shilajit
  • Citric acid

As stated earlier, Allergic Hypersensitivity Disease is also closely associated with Non IgE Mediated Immune Responses.

Compounds for Allergic Hypersensitivity Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

  • Resveratrol
  • Heparin Binding Agents – found in Nattokinase
  • Silicon – found in Shilajit
  • Chromium – found in Shilajit
  • Phosphatidylcholine
  • Proanthocyanidin – found in Prunella Vulgaris (Self-heal)
  • Chinese Salvia (Dan Shen)
  • Decanoic acid – found in MCT oil
  • Coconut – found in MCT oil
  • Vitamin K – found in several compounds in ReverseFX like Nattokinase and Prunella Vulgaris (Self-heal)
  • Omega 3 Fatty Acid – found in Sea Buckthorn
  • Beta-1,3-glucan
  • Vinpocetine
  • Iodine – found in Shilajit and Bladderwrack
  • Selenium – found in Shilajit
  • Copper – found in Shilajit
  • Molybdenum – found in Shilajit
  • Zinc – found in Shilajit and various other compounds in ReverseFX
  • Nickel – found in Shilajit
  • Vitamin E – found in several compounds in ReverseFX, specifically Sea Buckthorn
  • Maleic acid
  • Citric acid
  • Propolis
  • Licorice
  • Skullcap
  • Tannic acid – found in several compounds in ReverseFX (Pomegranate extract, Prunella vulgaris (Self-heal), Dan Shen Sea Buckthorn, Baical skullcap, Ashwaganda, Ginger root, Kudzu root)
  • Ginger
  • Rutin – found in Prunella Vulgaris (Self-heal)
  • Luteolin – found in Prunella Vulgaris (Self-heal)
  • Quercetin – found in Prunella Vulgaris (Self-heal)
  • Ursolic acid – found in Prunella Vulgaris (Self-heal)
  • Chitin/Chitosan – found in N-Acetyl Glucosamine (Nag)
  • Glucosamine – found in N-Acetyl Glucosamine (Nag)
  • Soy Bean – found in Nattokinase and Kudzu root, which Kudzu contains isoflavones, including puerarin (about 60% of the total isoflavones), daidzein, daidzin (structurally related to genistein)
  • Cranberry – found in D-Mannose
  • Palmitic Acid – found in Sea Buckthorn
  • Mannitol – found in Bladderwrack
  • Threonine – found in Shilajit
  • Valine – found in Shilajit
  • Leucine – found in Shilajit
  • Isoleucine – found in Shilajit
  • Proline – found in Shilajit
  • Lysine – found in Shilajit
  • Alanine – found in Shilajit
  • Folate – found in Sea Buckthorn
  • Vitamin C – found in various ingredients in ReverseFX, specifically Sea Buckthorn
  • Genistein – found in Nattokinase and structurally similar compounds found in Kudzu root
  • Rosmarinic acid – found in Prunella Vulgaris (Self-heal)
  • Lecithin – found in Phosphatidylcholine
  • Vitamin B’s – found in various compounds in ReverseFX
  • Vitamin K – found in several compounds in ReverseFX like Nattokinase and Prunella Vulgaris (Self-heal)
  • Anthocyanidin – found in Prunella Vulgaris (Self-heal)

An important gene associated with Allergic Hypersensitivity Disease is IL5 (Interleukin 5), and among its related pathways/superpathways are Innate Immune System and ERK Signaling.

Through binding to the interleukin-5 receptor, interleukin 5 stimulates B cell growth and increases immunoglobulin secretion – primarily IgA. It is also a key mediator in eosinophil activation.

Interleukin-5 has long been associated with the cause of several allergic diseases including allergic rhinitis and asthma, wherein a large increase in the number of circulating, airway tissue, and induced sputum eosinophils have been observed.

Compounds for Interleukin-5:

  • Quercetin – found in Prunella Vulgaris (Self-heal)
  • Punica granatum (Pomegranate extract)
  • Licorice
  • Emodin – found in Sea Buckthorn
  • Propolis
  • Kaempferol – found in Glycine max (Soy bean – Nattokinase), and Rosmarinic acid (Prunella Vulgaris/Self-heal)
  • Skullcap
  • Rutin – found in Prunella Vulgaris (Self-heal)
  • Luteolin – found in Prunella Vulgaris (Self-heal)
  • Ellagic acid – found in Pomegranate extract
  • Resveratrol

Lactose Intolerance

Lactose intolerance is when a person has symptoms due to a decreased ability to digest lactose, a sugar found in dairy products.

Lactose intolerance is not an allergy, because it is not an immune response, but rather a sensitivity to dairy caused by lactase deficiency. Milk allergy, occurring in only 4% of the population, is a separate condition, with distinct symptoms that occur when the presence of milk proteins trigger an immune reaction.

The principal symptom of lactose intolerance is an adverse reaction to products containing lactose (primarily milk), including abdominal bloating and cramps, flatulence, diarrhea, nausea, borborygmi, and vomiting (particularly in adolescents).

Lactose intolerance is a consequence of lactase deficiency.

An important gene associated with Lactose Intolerance is LCT (Lactase), and among its related pathways/superpathways are Glycosaminoglycan metabolism and Galactose metabolism.

Compounds for Lactose Intolerance (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

  • Calcium – found in various ingredients in ReverseFX, specifically Shilajit
  • Tannic acid – found in several compounds in ReverseFX (Pomegranate extract, Prunella vulgaris (Self-heal), Dan Shen Sea Buckthorn, Baical skullcap, Ashwaganda, Ginger root, Kudzu root)
  • Vitamin A – found in various ingredients in ReverseFX
  • Soy Bean (found in Nattokinase and Kudzu root, which Kudzu contains isoflavones, including puerarin (about 60% of the total isoflavones), daidzein, daidzin (structurally related to genistein)
  • Lecithin – found in Phosphatidylcholine
  • Alanine – found in Shilajit

Compounds for LCT (Lactase) Gene- From: DrugBank, HMDB, and Novoseek:

  • Vitamin C – found in various ingredients in ReverseFX, specifically Sea Buckthorn
  • Mannose
  • Beta-D-Glucose – found in Glycine max (Nattokinase)
  • Dextrose – through glucose-galactose transporter (SLC5A1)
  • N-Acetylglucosamine – through Beta-1,4-Galactosyltransferase 1 (B4GALT1 Gene), and UDP-Galactose-4-Epimerase (GALE Gene)
  • Manganese – found in Shilajit – through Beta-1,4-Galactosyltransferase 1 (B4GALT1 Gene)
  • Anti-Retroviral Agents – found in many ingredients in ReverseFX – through Galactose-1-Phosphate Uridylyltransferase (GALT Gene)
  • Palmitic Acid – found in Sea Buckthorn – through Lactalbumin Alpha (LALBA Gene)

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