LOW BRAIN HISTAMINE

Most citations used are taken from the NLM database and are in the public domain.

Down Syndrome is extremely complicated. Addressing one area of this metabolic, neurodegenerative disease will have little, if any effect and certainly, no benefit in the long term. However addressing multiple genes, neurotransmitters and biochemical disruptions at the same time will produce a lasting beneficial outcome.

One area, as mentioned above, is the radical imbalance in neurotransmitters. These are chemicals that are released at the end of a nerve fiber by the arrival of a nerve impulse and, by diffusing across the synapse or junction, causes the transfer of the impulse to another nerve fiber. This is how the neurons in the brain communicate.

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https://en.m.wikipedia.org/wiki/Neurotransmitter

Histamine is also present in the brain, where it acts as a critical neurotransmitters and throughout the body where it responds to allergens by triggering inflammatory mechanisms.

There is evidence that histamine may be deregulated in tissue as well. In some children with DS, it seems to be over reactive in the skin producing more severe allergic response than expected. This may result in hives, rashes, excess swelling, etc. Still other children seem to have very little reaction from histamine.

Recent studies have shown very low levels of the protein, HRF (histamine release factor) in the brain. This protein regulates the release of the neurotransmitter, histamine. Because the levels of this release factor are low, histamine in the brain is also low.

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The protein HRF is also known as TCTP. It was initially believed that FOXP2 ( a Forkhead box gene) was not active beyond the developmental phase but we now know that most genes belonging to this family actually remain active during life. Years ago, scientists believed that, because neurons do not divide, you were born with a lifetime compliment of them. That assumption was proven incorrect. New ineurons are produced regularly throughout natural life in the hippocampus. Some studies theorize that newly developed neurons may not migrate normally, but this does not seem to be the case.

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We have been able to locate this protein in a few natural substances. We know that they work on HRF as they are all natural histamine liberators. It is very possible that TCTP is present in many fruits in addition to those listed below but has not yet been identified. In fact, the regular ingestion of these specific fruits may well be one of numerous reasons why some children with DS have excellent speech while others have moderate to severe impediments. Many things, besides the low levels of HRF may effect speech in DS. One thing you need to understand is that histamine isn’t just a protein that responds to allergies, it is a very important neurotransmitter. The human brain requires it for numerous functions, one of which is human speech.

Another thing you need to keep in mind is that it is not histamine that is unavailable but the substance that releases histamine. FOXP2, is effected by the protein, HRF. So feeding your children foods high in histamine will not help. Further, Dr. Swenson has located information indicating that supplementing the diet with histamine may actually make things worse as in the presence of histamine, HRF shuts down. This reaction is similar to the reaction seen in examining the thyroid. TSH activates in the absence of thyroxine and becomes elevated triggering the thyroid gland to create and release its hormones. Once the thyroid releases thyroxine, or you supplement it, TSH levels drop in response.

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Presently, we are looking at ways to isolate the protein from fruits in much the same way Resveratrol is isolated from grape skin and Japanese Knotweed. This would make studying the protein in the DS animal brain much easier and enable future human use in the form of a properly dosed supplement. Isolating this protein may be difficult and costly. We have no information about this process that we can share at this time.
As a neurotransmitter, low brain histamine does explain numerous oddities in our children’s biochemistry, in particular, growth. The majority of children with DS, despite normal human growth hormone levels, remain very small in comparison with their same aged neuro typical peers. Despite treatment with human growth hormone, though growth is improved, most remain somewhat short in stature. Histamine is a prominent factor in growth.

Another point that is extremely important is that new neurons find the DS brain a hostile environment as there are many other genes and proteins that inhibit their development. It will be critical to address them (as we do now with TNI) or any new FOXP2 neurons will not survive.

There is no means at present, other than an autopsy, to determine if your child’s brain HRF is or isn’t low. The evidence is very clear that it is low in the majority of kids who 1) may have speech deficits, are short in stature, have poor immune response and vision problems. Though tests for some neurotransmitters have been developed, at present, histamine is not listed among them. In time, we are confident such a test will be developed.

READ THE FOLLOWING STUDIES

https://www.ncbi.nlm.nih.gov/pubmed/21618891
HRF is low in DS
Brain histamine levels are low in AD
A mutation – a fault – in the FOXP2 gene results in apraxia of speech, absence of speech and studdering along with other speech defects. But this article refers to the formation and migration of normal FOXP2 neurons. It may be that your child does have a mutation, if so then upregulating brain histamine may or may not result is improved speech. However, as we have seen, neuro histamine is involved in many important functions of the brain. It is important to address this deficit regardless of any benefit for speech.

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FOXP2 – The Human Speech Gene

https://ghr.nlm.nih.gov/gene/FOXP2

Evidence that low histamine during cortical development results in disruption of FOXP2 neurons does not necessarily mean that histamine, given exogenously, could result in the development of new FOXP2 neurons but it does not mean that there is nothing that can be done as it has been established that FOXP2 continues to express throughout life. One indicator is that there exist cases where speech has been fully restored after brain damage or stroke demonstrating that these neurons are either repaired or gradually replaced.

More importantly, histamine is a critical neurotransmitter that has not yet been addressed in DS, regardless if addressing it can restore or encourage speech. The brain will never function properly if we neglect this.

There are other histamine related problems in the DS brain, such as fewer receptors. This would be expected with low histamine as these are chemical receptors. H3 has been implicated in Alzheimer’s disease, Down Syndrome and other neurological diseases and disorders.

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Histamine-N-methyl transferase (HMT) is also low in DS. This enzyme inactivates the histamine neurotransmitter and in the presence of low histamine we would expect it to be low.
Basically, we have to ask ourselves whether all of these variations in brain histamine are a combined defect in the histamine neurotransmitter or if they are directly related to the low levels of HRF found in the DS.
At present, we theorize that the relationship between receptors, inactivator, neurotransmitter, lack of FOXP2 neurons, slow growth, poor immune response, poor vision, etc. may all stem from what may be a catalyst and that catalyst may be HRF. We do not presently know this but what we do know is that we must do whatever we can to try to correct this deficit.

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To begin at the beginning seems to be a logical target. We have a little more thinking to do before discussing whether or not a low histamine diet would be helpful. But it does seem likely that a diet high in HRF may be of some benefit. So let’s start there. The relationship between antihistamines and the higher incidence of Alzheimer’s disease is yet one more consideration. People with DS seem to live a lifetime exposed to what equals the result of antihistamine usage. It is likely, then, that low levels of histamine may related to cognitive decline in DS.

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The following are the highest readily available foods that actually contain TCTP (HRF). Adding them to your child’s diet may not encourage the production of FOXP2 neurons but it may raise brain histamine levels. We are continuing an extensive study of brain histamine but in the meantime, it certainly cannot be harmful to add these foods to your child’s daily diet and it may be beneficial. If it isn’t possible to obtain these fruits, both mango and full fruit papaya are available in capsule form.
FOODS THAT CONTAIN TCTP (HFR) DESIGNATED IN HUMAN BEINGS AS HISTAMINE LIBERATORS
TOMATOES
MANGO
PINEAPPLE
PAPAYA
At this point let’s not alter the diet other than to introduce histamine liberators as we are just not certain if exogenous histamine will reduce HRF further though one study indicated that it may.

SEE THE FOLLOWING RESEARCH
LONG TERM ANTIHISTAMINE USAGE AND AD
https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-201501287667

H3 RECEPTORS IN DS AND AD
https://www.ncbi.nlm.nih.gov/pubmed/10511950

FOXP2 EXPRESSES DURING ADULTHOOD Evidenced by the ability to learn foreign languages

http://neurosciencenews.com/foxp2-language-learning-genetics-2096/

TCTP IN EMBRYONIC VISUAL DEVELOPMENT
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852495/

LOW HMT IN DS
https://www.ncbi.nlm.nih.gov/pubmed/11880199

HISTAMINE AND FOXP2

https://neuraldevelopment.biomedcentral.com/articles/10.1186/1749-8104-8-4

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601999/…

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It is important to stay on top of copper levels. Copper completely destroys brain histamine. Copper is often high in DS but it is in free form and outside the cell. Copper is low within the cell. But supplementing copper is not the answer. The answer is to improve the transport of copper into the cells. Look for more on this on an upcoming article on GHK-cu, copper transport tripeptide. Summer of 2018.

THE FDA PROHIBITS EVEN INDIVIDUALS FROM MAKING MEDICAL CLAIMS FOR NUTRITIONAL SUPPLEMENTS. THE FOLLOWING MENTION OF NUTRIONAL SUPPLEMENTS IS PROVIDED BASED ONLY ON THE ATTACHED RESEARCH TO EXPLAIuN HOW THE HUMAN GENOME RESPONDS TO FOOD SUBSTANCES AND IS NOT INTENDED AS MEDICAL OR CURATIVE ADVICE.