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Urea/Nitric Oxide cycle disturbances

Literature and Connections on Ammonia Perturbations and their Impact on the Urea/Nitric Oxide Cycle and symptoms

Ammonia is also implicated in the detoxification of Cyanide - something that has recently been uncovered to be a potential player in ASD. For more information check out videos that I have with Dr. Christian Bogner on this subject at ResearchedElements.com. Ammonia can also be a contribution from protozoa. Cyanide can be both created and degraded by microbes in the gut.

Ammonia may not be an issue for everyone but I find it commonly an issue in ASD (it is a transient issue in many which makes it hard to pinpoint on testing and tends to scale with the digestive cycle) and implicated most often with fungal entities and can be further worsened by aluminum toxicity (Alpha-Ketoglutarate (AKG) inhibition). Ammonia can also be a feature of protozoa.

Aluminum toxicity also impairs AKG, and potentially BH41

Quorum Sensing in Fungi

(https://academic.oup.com/mmy/article/50/4/337/1178656)

(https://www.sciencedirect.com/.../pii/S0944501318300363)

We know the liver is generally taxed which also exacerbates the clearance of ammonia.

Teeth grinding and Giddy laughter are Key Symptoms in RETTS syndrome which is Clinically known as Hyperammonemia



Below is literature to support the Ammonia - Teeth grinding relationship

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1939-1676.1997.tb00101.x

Teeth grinding and Hyperammonemia / Urea Cycle Connections

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050374/?fbclid=IwAR1GOxZ42kYKU0e-0ADGyPnh0yHPk9iHkJfLMHugKCyieHWEbIVcfXyZL8o

https://www.merckvetmanual.com/special-pet-topics/poisoning/nonprotein-nitrogen-poisoning-ammonia-poisoning?fbclid=IwAR3FPSEmzd1Ena5g_zSbG8495y1mRUWelL8PSYyM9JJdffNdII19kw8k77Y

“Early signs include muscle tremors (especially of face and ears), protrusion of eyeballs, abdominal pain, drooling, passing large amounts of urine, and grinding the teeth. Tremors progress to lack of coordination and weakness. Fluid in the lungs leads to difficulty breathing and gasping. Horses may exhibit head pressing.”

https://www.researchgate.net/publication/227862775_Persistent_Hyperammonemia_in_Two_Related_Morgan_Weanlings?fbclid=IwAR2Xgh5kWAjPSgoipaBPrj3nP8afTCWc57pogZ1rsMphme-3-vpyyMiX-n0

We do know that RETT syndrome (Aka Genetic Hyperammonemia) which is a genetic condition that results in a high degree of ASD diagnosis is a condition implicated by HYPERAMMONEMIA and a key feature of this condition is Diurnal Bruxism (Teeth Grinding) and Giddy Laughter

Literature that describes that Rett Syndrome involves Giddy Laughter episodes (when too much ammonia meets too much nitrogen we get a backlog of nitric oxide (laughing gas) dissolved in blood)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527512/?fbclid=IwAR2BEWnOGtAC3T44wk3gwH7iX2ALm638xXLMZ19EDHKcx_X1T_7EtWRO6wA

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351186/?fbclid=IwAR303gES06BXMXKsSk_G4pRnxR9MUwqhTj1JNDTYpQPm-asPAZOAlZC8wIs

https://www.mayoclinic.org/diseases-conditions/rett-syndrome/symptoms-causes/syc-20377227?fbclid=IwAR2EQVrL9zw2cbAGWme86D5qkWLW8yXt47IPWUw5xSvCsyLEyL4GQ5sQAJM

Below is Literature to suggest the effect of Ammonia on Sleep

https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.24741?fbclid=IwAR1rvqeoij2DjAgTlpvd4HWiFQD0QGiFvaG9f5kauJU0kltiAkhihBtDpR8

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442851/?fbclid=IwAR05RH3AKxgI39pBj8zsIHxUxYEezyvrfKrHL06avkjQHRvD8afgcD-ggp4

https://jintensivecare.biomedcentral.com/articles/10.1186/2052-0492-2-22?fbclid=IwAR21Nx5v9tV2C5B8KHEXeK0udbmz139mqSJijtHDll_dYfTM2sum4ifIWfA

If you do some more investigation you will realize the connection between sleep paralysis (a condition where you wake in extreme fear and terror suddenly) and GABA. Typically this sleep paralysis can be brought on from eating foods with MSG in neurotypical people too.

We know the connection between ammonia excess affecting the GABA - GLUTAMATE cycle.

If you do some further investigation you will find a relationship between certain Epilepsy and Bruxism and also we know that Fungal Infections can be a significant cause for seizures / epilepsy, and we know that ammonia may be the cause.

https://pubmed.ncbi.nlm.nih.gov/15210903/

We know Gelastic - Laughing Seizures have their own name but in my experience this Giddy / Laughing Phenomenon occurs when Too much nitrogen is present in the presence of high ammonia

It causes excess amounts of Nitric Oxide to be dissolved in the blood - inducing this laughing event (Nitric Oxide is Laughing gas). The Nitric Oxide Dump is just adjacent to the urea cycle - and this ammonia issue.

(see cycle Picture for NOS/ urea relationship)

In my experience from my own son and in recommending supplements based on these behaviors

Teeth grinding

Night Waking

Elevated Ammonia on Testing

Inappropriate / Excessive Unexplained Laughter / Giddiness (caused by nitrogen + ammonia overload)

The addition of Ammonia processing agents to help the urea cycle has helped to either stop these symptoms or help them. I have also found that activated charcoal has assisted in binding ammonia.

Helping to heal the intestinal permeability, supporting the liver, and removing aluminum toxicity may also help the issues.

Ammonia Processing Support - we have developed a great tasting formula which combines amino acids for urea cycle / nitric oxide support and includes sodium butyrate as well Ammonia Away from Researched Elements.

Remember there is no Urea Cycle in the brain - likely the ammonia buildup is exacerbated by issues in the brain which prevent the release of ammonia. Therefore AKG may be of assistance there, and the arginine and citrulline seem to help in the liver, these are all in our formula.

Sodium Butyrate is a great tool for assisting ammonia surges that reach the brain however the issue with Sodium butyrate is that it has a very strong non ideal taste and even has a slight burning / tingling when ingested. We have managed to create a formula that is palatable which includes sodium butyrate in our Ammonia Away supplement.

Note that Nitric Oxide Issues may also be implicated in B12 status - 

In particular it has been noted that Giddy laughter was mitigated with the use of Adenosylcobalamin

See literature https://www.sciencedirect.com/science/article/abs/pii/S0891584909001750

References:

1. Mujika JI, Ugalde JM, Lopez X. Aluminum interaction with glutamate and α-ketoglutarate: a computational study. J Phys Chem B. 2014 Jun 19;118(24):6680-6. doi: 10.1021/jp502724w. Epub 2014 Jun 10. PMID: 24874214. 

Categories: ASD autism Tags: ammonia nitric oxide cycle

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