Featured in the Autumn 2017 edition of the Autism Eye Magazine. Written by Stella Chadwick.
Some children with autism can present with “allergic-like” symptoms, when there is no obvious elevation in serum level of IgE or chronic urticaria, as expected during a typical histamine reaction. There appears to be non-allergic mast cell activation, most likely in response to environmental and stress triggers, which in turn contributes to inflammation. In some children with autism, histamine intolerance may be contributing significantly to symptoms generally associated with ASD.
What is Histamine?
Histamine is a biogenic amine and small quantities are present in almost all foods, which usually cause no problem. There is always a certain amount of histamine in circulation in plasma (the fluid part of the blood) and the level changes throughout the day. It’s generally high in the daytime and low during sleep and extremely low during deep sleep. Histamine acts as a modulator of several neurotransmitters in the brain and plays a key role in keeping the body awake and alert. If you have a child, who really struggles to fall asleep, then suspect high histamine levels as a potential contributory factor. Another key job that histamine carries out is to stimulate the secretion of acid in the stomach. Adequate stomach acid is fundamental to digestion and the absorption of vitamins and minerals. Histamine also protects the body against pathogens such as insect bites, toxic chemicals, nettle stings and the like. In such scenarios the body releases a large amount of histamine to go to the site, causing blood vessels to widen so that white blood cells can move quickly to the area of assault to help repair and protect it. As part of the histamine reaction, and in order to get the pathogen out, the tissue surrounding the affected area secrete fluids (a runny nose for instance). If there is a lot of histamine in the gut then stools may regularly contain mucous, which is part and parcel of the histamine reaction. Table 1 shows the key signs of histamine intolerance.
How is Histamine manufactured?
Histamine is manufactured and stored in a number of cells in the body, particularly mast cells that exist throughout body tissues, especially mucous tissue. Mast cells can also get activated during times of stress and CRH (Corticotropin-Releasing Hormone) is released causing mast cells to liberate histamine. In theory cortisol contributes to lowering histamine levels, but in those cases where adrenals have been working hard for an extended period of time, as is the case with many people with an autism diagnosis, cortisol levels tend to be low and so CRH stays high, contributing to releasing inflammatory cytokines such as IL6 and IL8. Of significance in clinical practice is the fact that histamine can be activated as a result of infections, whether bacterial, viral or parasitic and as a result of toxic load. When a large amount of histamine is released, the body tries to balance it via a negative feedback loop and produces adrenaline to lower histamine levels – so in cases of chronic infections there can be chronically high levels of adrenaline interfering with mood, sleep, and intellectual development. It’s important to note that infections and chronic stress can contribute to high histamine levels despite a diet low in histamine.
High doses of histamine are toxic to all people and the tolerance level varies between individuals based on genetics, disease, gut damage and disturbed gut microbiome, and use of certain medication. In some cases, high histamine levels are the result of the inability of the body to break histamine down adequately.
How is histamine broken down?
In the CNS (Central Nervous System) histamine is broken down by HMT (Histamine Methyltransferase) enzyme. This means that impaired methylation can contribute to high histamine levels. In some cases, methylated B vitamins and supplements such as DMG and TMG can help reduce histamine levels. In the digestive tract, histamine is broken down by DAO (Diamine Oxidase) enzyme, which tends to be low in those with allergies or auto-immune conditions. A number of studies have shown that DAO is dramatically increased by the consumption of oleic acid found in olive oil. Interestingly during pregnancy DAO production can go up by 500 to 1000 times, in order to create a metabolic barrier to prevent the exposure of excessive histamine to the foetus. If during pregnancy, migraines and allergies seem to disappear or diminish, then consider low DAO as a contributing factor to the high histamine levels both in the mother and the baby. In cases where DAO levels remain low during pregnancy complications such as premature birth or gestational diabetes can occur. DAO tends to occur mainly in the lining of the intestine, as well as placenta kidneys and the thymus gland. HMT is more prolific and occurs in the stomach, lung, spleen, kidney, thymus and particularly the brain.
So how do we normalize histamine levels?
Remove problem foods
Large quantities of histamine result from microbial activity during the rotting of food and during the manufacture of cured, smoked and fermented foods such as cheese, cured meats, vinegar, alcoholic drinks, sauerkraut, soya sauce etc. Microbial enzymes convert histidine to histamine. Leftover food can have significant levels of histamine and the levels will vary depending on how fast this microbial metabolism takes place. It’s important to note that histamine levels can be excessively high well before the food is spoilt. Some foods have naturally high levels of histamine. Table 2 has an outline of the key foods to look out for. Some cosmetic and toiletries also contain histamine-releasing substances as such cinnamaldehyde, Balsam of Peru, benzoates of any type, and sulfites and dyes. One of the clearest signs of histamine intolerance is a bad reaction to having fermented foods such as sauerkraut.
Foods and supplements, which may help with managing histamine levels
Consumption of foods high in quercetin, a bioflavonoid found in ginger, garlic and onions, elderberries, bee pollen, and fennel leaves, can help lower histamine levels. Quercetin stabilizes the cell membrane of mast cells and prevents them from spilling their load of histamine into the surrounding tissue. DAO needs copper to function, so keeping normal copper levels is essential – be mindful of excessive zinc supplementation. There are also supplements such as DAOsin containing DAO to help break down histamine from food but will not increase levels of DAO in the gut. Carnosine is a naturally occurring dipeptide and has been shown to protect mast cells from degranulation and histamine release. Supporting the adrenals is also important given the feedback loop discussed earlier where adrenaline is released to negate the histamine in the system. Other supplements that may lower histamine levels are those containing mangosteen which is both an anti-inflammatory and a histamine inhibitor. Black seed oil and nettle tincture can both help reduce histamine levels as can frequent dosing of vitamin C. When considering probiotics it’s important to ensure that supplements contain the right strains. There are certain probiotic strains which have been shown to reduce histamine levels such as Lactobacillus rhamnosus, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus plantarum, and possibly Lactobacillus reuteri. There are some strains which have been shown to promote the production of histamine and should be avoided. These include; Lactobacillus casei and Lactobacillus bulgaricus.
Histamine issues can come from a number of sources and can be a problem for a subset of children with autism, regardless of whether or not a diet is low in histamine foods and drinks. It is important to ensure that underlying infections and pathogens are addressed and that all measures are taken to help manage symptoms to reduce histamine and control the inflammatory cascade that it can promote.
|SIGNS OF HISTAMINE INTOLERANCE|
· Difficulty falling asleep, easy arousal
· Vertigo or dizziness
· Arrhythmia, or accelerated heart rate
· Difficulty regulating body temperature
· Nausea, vomiting
· Abdominal cramps
· Nasal congestion, sneezing, difficulty breathing
· Abnormal menstrual cycle
· Tissue swelling
· Bad reaction after eating fermented food like sauerkraut
· Physical reaction like hives or emotional reaction like anxiety and hyperactivity if consuming citrus foods