RESEARCH LINKS AUTISM WITH HISTAMINE, INFLAMMATION, AND MAST CELL ACTIVATION:

The study of histamine has been attracting quite a bit of attention over the last few years — and not just in relation to seasonal allergies or insect bites. The compound is also associated with a variety of other health complaints, from migraines and depression to schizophrenia. And now scientists have discovered another surprising connection to the naturally occurring chemical: autism. The Role Histamine Plays in Immune Response

When we come in contact with an allergen that we have a sensitivity to — like pollen or we’re stung by an insect — the body releases histamine to overcome the threat. A series of physiological reactions occur: blood vessels dilate, while mast cells (a type of white blood cell) are activated to attack the invader.

If we experience an angry rash, itchy eyes or swelling, that’s histamine at work. Usually, the reaction subsides quickly once the threat is over. But sometimes, when the body is exposed to an excess of histamine — either through the ingestion of high-histamine foods or with excessive production by the body — an intolerance to the chemical may develop, which can lead to asthma, anxiety, digestive disorders, mood swings, aggression, fatigue and much more. In fact, Dr. Theoharis Theoharides, a mast cell researcher and head of the Molecular Immunopharmacology and Drug Discovery Laboratory at Tufts University, has even found mast cell activation may be the root cause of autism in many children. The Connection Between Autism and Brain Inflammation

Autism spectrum disorders (ASDs) now affect as many as 1 in 45 children — and the numbers are rising. Considered a neurodevelopment disorder, autism is characterized by varying degrees of dysfunctional communication and social interactions, repetitive and stereotypic behaviors, as well as learning and sensory deficits. [source] Researchers are scrambling to pinpoint the reason for this disturbing trend, but the disorder has proven to be incredibly complex and treatment options are limited.

A promising study published during the summer of 2016 in Translational Psychiatry may shed some much needed light on the root cause of the disorder — and how to address it.

Dr. Theoharides and his colleagues — in collaboration with Tufts University School of Medicine, Sackler School of Graduate Biomedical Sciences, and the Department of Child Psychiatry at Harvard Medical School — believe they may have uncovered a significant cause of the core symptoms of ASD. Dr. Theoharides is considered an expert in his field and is within the top five percent of most quoted authors in scientific papers.

According to the study:

“Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB [blood brain barrier] permeability.”

The findings indicate that levels of pro-inflammatory molecules interleukin (IL-1B, IL-6, IL-17) and tutor necrosis factor (TNF) are elevated in the brain, spinal fluid and blood of autistic patients and increase when the individual is under stress. These molecules are produced directly by mast cells.

Another paper published by Dr. Theoharides in the journal Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease found a similar correlation between mast cell activation and neurodevelopment issues:

“A number of papers, mostly based on parental reporting on their children’s health problems, suggest that ASD children may present with “allergic-like” problems in the absence of elevated serum IgE and chronic urticaria. These findings suggest non-allergic mast cell activation, probably in response to environmental and stress triggers that could contribute to inflammation. In utero inflammation can lead to preterm labor and has itself been strongly associated with adverse neurodevelopmental outcomes. Premature babies have about four times higher risk of developing ASD and are also more vulnerable to infections, while delayed development of their gut–blood–brain barriers makes exposure to potential neurotoxins likely. Perinatal mast cell activation by infectious, stress-related, environmental or allergic triggers can lead to release of pro-inflammatory and neurotoxic molecules, thus contributing to brain inflammation and ASD pathogenesis, at least in a subgroup of ASD patients.”

Likewise, this study study in Cellular and Molecular Neurobiology discovered that “Histamine is one of the few central nervous system neurotransmitters found to cause consistent blood–brain barrier opening” which is a factor in inflammation, cerebral edema and what Dr. Theoharides calls “allergy of the brain” in ASD patients.

Moreover, when large amounts of histamine are present, the body triggers the production of epinephrine (adrenaline) to correct the imbalance. Adrenaline then sparks a flight or fight response within the body. If this heightened state of stress becomes chronic, it interferes with stomach acid production and overall digestion — leading to parasites, pathogenic bacteria and food sensitivities. The body also dumps magnesium and zinc into the muscles to prepare for a quick reaction. This in turn creates deficiencies of these important minerals, which are crucial for the immune system and neurological development. Disruption of sleep, anxiety, learning disabilities and malabsorption issues soon follow. Reducing Mast Cell Activation

To reduce mast cell activation and subsequent inflammation, several approaches are effective. One is to consume a low-histamine diet. Another is to use carnosine and methylated B vitamins. To breakdown histamine in the digestive tract, supplementing with diamine oxidase (DAO) may be necessary if the individual is susceptible to low DAO levels through genetic heritage or diet. Many times, people who are deficient in DAO also suffer from allergies and auto-immune disorders, both of which are common in ASD individuals.

Dr. Theoharides has also examined the possible use of luteolin and other bioflavonoids such as quercetin for their calming properties in relation to mast cell activation and brain inflammation.

In the paper Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders, Dr. Theoharides concludes:

“Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD.”

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RESEARCH LINKS AUTISM WITH HISTAMINE, INFLAMMATION, AND MAST CELL ACTIVATION: