The CYP450 Medication, Inflammation, and Histamine Connection
I have been wanting to write for some time on the CYP450 medication, inflammation, and histamine connection, as this information has been so important in my own pathway to recovery.
I have had histamine intolerance all my life, but developed mast cell activation disorder, when put onCYP450 mediated (and in particular CYP2D6 related medication).
Simplistically, I have CYP2D6 genetic mutation, which pushed my body into oxidative stress, that resulted in chronic inflammation markers (mine were c-reactive protein, and ceruloplasmin).
There are many paths to histamine intolerance and mast-cell activation disorder and my path is just one of them. Medication intolerances, however, are extremely common once firmly on that pathway.
There are a number of reasons why medication may be problematic with histamine intolerance, and I am only addressing one of them, which is the CYP450 medication, inflammation, and histamine connection
Histamine is an organic compound, produced by and stored inside tissue mast cells and blood basophils. There are two major mechanisms of histamine release – an active and a passive mechanism.
The active mechanism is evoked by an antigen-antibody response, such as an infection, which triggers the organised release of histamine from its granules into the tissues without cell death.
The passive mechanism, also known as cytotoxic, is evoked when a noxious stimuli, damages the cell membrane and everything stored inside the cell is released, including histamine. Histamine is released as the cell dies.
Whether active or passive, the integrity of the cell membrane, plays a major role in the release of histamine, and this is why mast-cell stabilising foods (and even medications) can be helpful.
Free radicals are extremely harmful to the cell membranes, and provoke the release of histamines from mast cells and basophils. Studies show that free radicals interact directly with the cell membrane, eliciting an active release of histamine without actually damaging the cell. This is part of a complex sequence of events that occur at sites of inflammation.
Despite the fact that free radicals are known to be harmful to cells, they elicit an active (without cell death) release of histamines. This means that somehow receptors on the outer membrane, recognise these free radicals and provoke the organised release of histamine without cell death.
This may be physiologic, because when the body faces an infection, white blood cells produce free radicals to destroy bacteria, and the same free radicals elicit the release of histamine, which promotes blood flow to the area of infection, and triggers the calls for more white blood cells.
Prescription drugs that are metabolised by Cytochrome P450 genes (whether you have a genetic mutation or not) have been shown to generate oxidative metabolites that act as free radicals. Other substances (such as some Omega 6 fatty acids) can also cause oxidative stress.
Several studies demonstrated that in mast cells, these free radicals can provoke the release of histamine, mostly through an active mechanism (that does not result in cell death but releases histamines as a protective response).
Studies show that if natural anti-oxidants, and in particular glutathione, is present in enough quantities, it can protect mast cells against free radical damage, and consequently halt histamine release. This suggests as a minimum that glutathione can improve the tolerance of medications, and halt any histamines released by them.
Dr Ben Lynch, and Dr Bill Walsh, both leading methylation experts, also support this hypothesis, as they believe that until the glutathione cycle is optimised, any methylation interventions will be unsuccessful.
In summary, the CYP450 medication, inflammation, and histamine connection is proven. Glutathione provides a proven protective measure when taking CYP450 medication.
Personally, my mast-cell activation symptoms have been greatly helped by increasing my glutathione levels. When I started this journey I could not tolerate quercetin, vitamin c, and a very broad range of foods. Raising my glutathione levels has gradually allowed me to tolerate a broader range of foods, my body is less sensitive to a broad range of environmental triggers, and my mast-cell activation disorder is effectively in remission.
- 12/01/2015 • Drug Tolerance Testing and Why You Should Not Use Online Report Readers
- 07/21/2015 • A Bio-Individual List of Histamine Inhibitors
- 07/02/2015 • Glutathione: A List of the Most Potent Inhibiting and Inducing Anti-oxidant Foods and Bioactives
- 06/25/2015 • CYP450 Enzymes: A Complete List of the Most Potent Inhibiting and Inducing Foods and Bioactives