lassesen 9:21 am on December 17, 2022  

Exploring DAO / Mast Cells / Histamine Issues

In a dialog with a reader, the question was raised “If you assume that these issues are due to low levels of DAO, are the low levels dues to an absence of precursors or the bacteria producing these precursors?“

This type of issue is often co morbid with ME/CFS and IBS.

See this update Mast Cell Moderators — non-drugs and suspect bacteria also

Diamine oxidase, also known “amine oxidase, copper-containing, 1”, formerly called histaminase, is an enzyme involved in the metabolism, oxidation, and inactivation of histamine and other polyamines such as putrescine or spermidine in animals. It belongs to the amine oxidase family of amine oxidase enzymes.

Wikipedia

The Kyoto Encyclopedia of Genes and Genomes technical description is ENZYME: 1.4.3.22

Product (produces)Substrate (Consumes)
(imidazol-4-yl)acetaldehyde;
NH3 [CPD:C00014] – Ammonia
H2O2 [CPD:C00027] – Hydrogen Peroxide		histamine [CPD:C00388];
H2O [CPD:C00001]; – Water
O2 [CPD:C00007] – Oxygen
Note: Ammonia and Hydrogen Peroxide are both inhibitors of some bacteria

.The obvious factors to consider are: being hydrated (plenty of water in the body) and oxygen (Saturated O2 should be 98 or better).

A more obtuse speculation is that bacteria that does not like ammonia or hydrogen peroxide are somehow impacting the production of this enzyme.

Over Consumption Elsewhere?

Like most things in the body, one enzymes may have multiple purposes. What if a different process is over-consuming this enzyme?

Looking at the pathways that it is involved with:

Arginine and proline metabolism https://www.kegg.jp/pathway/ec00330+1.4.3.22

Histidine metabolism https://www.kegg.jp/pathway/ec00340+1.4.3.22

Tryptophan metabolism https://www.kegg.jp/pathway/ec00380+1.4.3.22

So high levels of Tryptamine and/or Putrescine may result in over consumptions. I went to the new AI expert – ChatGPT, which gave me the following answers:

Tryptamine is a compound that is produced by the breakdown of the amino acid tryptophan in the body. High levels of tryptamine in the body can be caused by a number of factors, including:

  1. High tryptophan intake: Consuming a diet that is high in tryptophan can lead to increased production of tryptamine in the body.
  2. Certain medications: Some medications, such as serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs), can increase the production of tryptamine in the body.
  3. Genetic factors: Some people may have a genetic predisposition to produce higher levels of tryptamine due to variations in their DNA.
  4. Tissue damage: Tryptamine can be produced as a result of tissue damage, such as from injury or surgery.

Putrescine is a compound that is produced by the breakdown of proteins in the body. High levels of putrescine in the body can be caused by a number of factors, including:

  1. High protein intake: Consuming a diet that is high in protein can lead to increased production of putrescine in the body.
  2. Bacterial infections: Some types of bacteria, such as Escherichia coli and Proteus mirabilis, produce putrescine as a byproduct of their metabolism.
  3. Tissue damage: Putrescine can be produced as a result of tissue damage, such as from injury or surgery.
  4. Certain medications: Some medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), can increase the production of putrescine in the body.
  5. Genetic factors: Some people may have a genetic predisposition to produce higher levels of putrescine due to variations in their DNA.

What we have in common is: a result of tissue damage, such as from injury or surgery. So, a person with Crohn’s Disease or other conditions that has tissue damage would have over production of both of these. To this situation, we have the concurrent consumption of Nonsteroidal anti-inflammatory drugs (NSAIDs) which could contribute to a feedback loop. Common NSAIDs include: Aspirin, Ibuprofen, Naproxen, Celecoxib and Diclofenac.

So how can we reduce these levels, again, I went to the new AI expert on the block and got:

Tryptamine is a compound that is produced by the breakdown of the amino acid tryptophan in the body. It is not possible to directly reduce tryptamine levels in the body through dietary changes, as tryptamine is produced through the breakdown of tryptophan. However, there are some steps you can take to reduce tryptophan levels in the body, which may in turn lower tryptamine production:

  1. Reduce intake of foods high in tryptophan: Some foods that are high in tryptophan include turkey, cheese, nuts, seeds, and tofu. Limiting your intake of these foods may help to reduce tryptophan levels in the body.
  2. Eat a balanced diet: Ensuring that you are consuming a varied and balanced diet can help to maintain healthy tryptophan levels in the body.
  3. Get enough sleep: Adequate sleep is important for maintaining healthy tryptophan levels in the body.
  4. Manage stress: Chronic stress can lead to increased tryptophan levels in the body. Practicing stress management techniques such as meditation, yoga, or deep breathing can help to reduce stress and lower tryptophan levels.

Putrescine is a compound that is produced by the breakdown of proteins in the body. It is not possible to directly reduce putrescine levels in the body through dietary changes, as putrescine is produced through the breakdown of proteins. However, there are some steps you can take to reduce protein intake, which may in turn lower putrescine production:

  1. Reduce intake of high-protein foods: Some high-protein foods include meat, dairy products, beans, and nuts. Limiting your intake of these foods may help to reduce protein intake and lower putrescine production.
  2. Eat a balanced diet: Ensuring that you are consuming a varied and balanced diet can help to maintain healthy protein levels in the body.
  3. Get enough sleep: Adequate sleep is important for maintaining healthy protein levels in the body.
  4. Manage stress: Chronic stress can lead to increased protein breakdown in the body. Practicing stress management techniques such as meditation, yoga, or deep breathing can help to reduce stress and lower protein breakdown.

This boils down to: reduce stress, get sleep, and removing some foods from the diet.

Reducing by Bacteria?

I again asked ChatGPT with the following responses:

Tryptamine is a compound that is produced by the breakdown of the amino acid tryptophan in the body. It is not a common source of energy for bacteria and is not essential for their growth and survival. Some bacteria may be able to consume tryptamine as a source of nitrogen, but it is not widely studied.

Putrescine is a compound that is produced by the breakdown of proteins in the body. Some bacteria are able to consume putrescine as a source of energy and nitrogen.

Examples of bacteria that can consume putrescine include:

  1. Escherichia coli: E. coli is a type of bacteria that is found in the intestinal tract of humans and animals. It is able to consume putrescine as a source of energy and nitrogen.
  2. Proteus mirabilis: P. mirabilis is a type of bacteria that is found in the intestinal tract of humans and animals. It is able to consume putrescine as a source of energy and nitrogen.
  3. Pseudomonas aeruginosa: P. aeruginosa is a type of bacteria that is commonly found in soil and water. It is able to consume putrescine as a source of energy and nitrogen.
  4. Klebsiella pneumoniae: K. pneumoniae is a type of bacteria that is found in the respiratory tract of humans and animals. It is able to consume putrescine as a source of energy and nitrogen.

Escherichia coli is especially interesting because there are 30+ studies on an E.Coli probiotics helping a variety of conditions including: Inflammatory bowel disease (IBD), Crohn’s disease and irritable bowel syndrome. Unfortunately, 16s microbiome analysis does not report E.Coli levels (which would be expected to be low).

E.Coli is available as a probiotic (good strains!)

Proteus mirabilis is similarly poorly reported with 16s, shotgun (Xenogene) reports that it is likely seen in 56% of samples. However, the special handling done by BiomeSight, appears to detect it around the same rate.

With our special studies of MCAS, we do find Pseudomonas (parent of Pseudomonas aeruginosa) being statistically significant as too low.

This suggests that some people with MAST cell/histamine issues may benefit from either of the E.Coli probiotics: Mutaflor (E.Coli Nissle 1917) or Symbioflor-2.

Naïve Diet Changes?

I went to Microbiome Prescription and picked 3 genus (Pseudomonas, Escherichia, Proteus ) cited above to see what would encourage their growth (and thus reduce levels of Putrescine). The results are below and interesting: especially the to-avoid probiotics.

Items to TakeItems to Avoid
iron
lactulose
glucose (sugar)
rhubarb
symbioflor 2 e.coli probiotics
* US Source
* World Wide Source

oregano (origanum vulgare, oil) |
foeniculum vulgare (Fennel)
lactobacillus plantarum (probiotics)
lactobacillus casei (probiotics)
lactobacillus rhamnosus gg (probiotics)

Bottom line

This is an exploration on the infrastructure around DAO and thus mast cell issues. The most likely explanation is that DAO is being consumed by alternative processes connected to Putrescine and Tryptamine. Over production of these appear to be associated with GI injury. Reduction of these competitors may be possible by diet and by the use of E.Coli probiotics. Common lactobacillus probiotics may make things worse. Thus “histamine-free probiotics” may actually encourage the competitors (at least one brand contains lactobacillus plantarum )