Histamine Intolerance and Your Brain: Sleep, Mood and More

Are you wondering how histamine intolerance affects your brain? By now you’re likely aware of the effects of histamine on your overall health and how an excess of histamine is the reason behind your chronically dripping nose, digestive issues like bloating and cramps, and other irritating allergic reactions like a rash, itchy eyes and a scratchy throat. You already know that histamine forms as part of many essential processes related to your immune response, and why the foods you eat trigger histamine, but did you know that histamine plays a crucial role in your brain, too?Surprisingly, the histamine response in your brain that can have such a profound effect on your mood, ability to concentrate, and overall brain function. Today, you're going to discover the link that living with high histamine has with your sleep troubles, emotional imbalances and stress responses. Histamine in the brain Your brain is constantly receiving signals from the environment via inputs from your five senses. The brain doesn’t simply receive and process them; it takes four complex systems, called the aminergic systems, to process the information and ensure it goes through the correct channels. One of these systems is known as the histaminergic system, which involves a histamine-mediated process. The role of histamine here is one of homeostasis, or balance. It acts as a modulator of the stimuli received relating to1: The sleep-wake cycle Motivation and goal seeking behaviors Satiety, feeding behaviors and taste perception Neurotransmitter regulation Addictive behaviors Memory formation Stress Pain perception Those all seem pretty important, don’t they; and with this in mind, you can begin to paint a picture of why an increase in your histamine load affects your brain so profoundly. But where in the brain does this happen?The histamine found in brain tissue comes from two major pools, namely mast cells and neurons. Mast cells are relatively scarce in the brain, therefore the primary source of histamine is found in neurons. More specifically, these histamine-releasing neurons are exclusive to just one region of the brain, known as the hypothalamus2. It is from this location that histamine spreads to other areas of the brain.When histamine binds to the receptors located in other brain regions, it causes an excitatory effect, one which is amplified even further during periods of wakefulness3. This means that histamine is independently over stimulating areas of the brain. To break down histamine in the brain and prevent this excitatory mechanism from running rampant, the HNMT enzyme (not DAO, that you’ve likely heard about so often) comes into play. HNMT breaks down histamine by forming a t-type methylhistamine, which is then broken down even further by two enzymes called monoamine oxidase B (MAOB) and aldehyde dehydrogenase4. Now, looking at the list of functions above, and having and idea of histamine’s importance, let’s take a deeper look at the symptoms caused by histamine in the brain. Histamine and sleep You already know that histamine is responsible for wakefulness, so there is little wonder why too much histamine increases the risk of sleeplessness and sleeping disorders like insomnia. It's interesting to note that more than half of all of the over-the-counter sleep aids contain a histamine receptor blocking agent, to reduce the effects of histamine in sleep disorders5. Histamine and motivation Histamine plays a role in motivation and reward mechanisms in the brain6. The association has been studied in exercise capacity, where the response to an increase in histamine increases motivation to complete tasks, and has a positive influence on goal seeking behaviors. Histamine, hunger and eating behaviors Hunger is a survival mechanism, which the body uses to stimulate food seeking as a means to meet the metabolic and energy demands of the body. We have known about the link between histamine and feeding cycles since the 70s - there’s a distinct inverse correlation between histamine levels and food intake. As histamine increases, so does appetite and feeding behavior7. Histamine and neurotransmitters Histamine itself is an important neurotransmitter, which has an influence on other neurotransmitters (chemical messengers). This is why histamine has implications towards neuropsychiatric conditions like depression, schizophrenia and even ADHD when histamine levels are high8,9,10. Histamine an addictive behaviors In studies on rats, it has been found that alcohol dependence may be influenced by higher brain histamine levels, and that therapies used to block particular brain histamine receptors may be a safe and effective treatment for alcohol abuse disorders11. Histamine and memory Histamine has been shown to have a positive effect on memory, and there’s even evidence to suggest that higher brain histamine levels may offer protection against Alzheimer’s Disease12. Histamine and stress Activation of the stress response has been associated with the triggering of itching; a well-known symptom of allergic and histamine reactions. While stress itself doesn’t actually cause allergies, the chemicals released into your body as a result of stress increases the production of histamine, this in turn aggravating the symptoms13.Fortunately, there is something you can do about these brain-influencing actions of histamine. A low histamine diet: your most powerful weapon By following a low histamine diet, you can reduce the amount of histamine your body has to contend with. You can download my complete guide on this for free: Get the FREE eBook In addition to this, there is another powerful way your diet can impact your histamine intolerance, and act directly on your brain. Research has shown that a compound called nitric oxide (NO), which you can find in food, can help to inhibit the production of histamine directly in the hypothalamus14. Nitric oxide boosting foods include: Beetroot (one of the best sources of dietary NO) Garlic Pomegranate Meat Nuts and seeds Histamine has a serious and widespread effect on the body, and high levels can be debilitating, affecting every aspect of your quality of life. The first step to getting your histamine under control is to focus on your diet, not only to remove those histamine-offending foods, but to add foods into your meals that help to break it down.If you’re struggling with histamine symptoms that affect your brain, it’s essential to add these nitric oxide-rich foods to your diet. These foods can be found as part of the allowed foods in my free guide to histamine intolerance and can assist both your brain and other symptoms. Click below to get the free e-guide now! Get the low histamine guide!   References: Brown, R. E., Stevens, D. R., & Haas, H. L. (2001). The physiology of brain histamine. Progress in Neurobiology, 63(6), 637–672. https://www.sciencedirect.com/science/article/pii/S0301008200000393Shan L, et al. Interactions of the histamine and hypocretin systems in CNS disorders. Nat Rev Neurol . 2015;11(7):401–413. https://www.ncbi.nlm.nih.gov/pubmed/26100750Bolam, P., & Ellender, T. Histamine and the striatum. Neuropharmacology. Volume 106, July 2016, Pages 74-84. https://www.sciencedirect.com/science/article/pii/S0028390815300599#bib5 Haas HL, et al. Histamine in the nervous system. Physiol Rev . 2008;88(3):1183–1241. https://www.ncbi.nlm.nih.gov/pubmed/18626069Naganuma F, et al. Histamine N-methyltransferase regulates aggression and the sleep-wake cycle. Sci Rep . 2017;7(1):15899. https://www.ncbi.nlm.nih.gov/pubmed/29162912Loy, B. D., & O’Connor, P. J. (2016). The effect of histamine on changes in mental energy and fatigue after a single bout of exercise. Physiology & Behavior, 153, 7–18. https://www.sciencedirect.com/science/article/abs/pii/S0031938415301463Provensi G., et al. (2016) Histamine and Appetite. Histamine and Appetite. In: Blandina P., Passani M. (eds) Histamine Receptors. The Receptors, vol 28. Humana Press, Cham. https://link.springer.com/chapter/10.1007/978-3-319-40308-3_15Sadek, B., et al. Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases. Behavioural Brain Research. Volume 312, 1 October 2016, Pages 415-430. https://www.sciencedirect.com/science/article/pii/S0166432816304168 Silk, T. Chapter 13 - New Frontiers: Neurobiology of Sleep in ADHD. Sleep and ADHD: An Evidence-Based Guide to Assessment and Treatment. 2019, Pages 331-353. https://www.sciencedirect.com/science/article/pii/B9780128141809000132Ellenbroek, A., et al. Do Histamine receptor 3 antagonists have a place in the therapy for schizophrenia? Current Pharmaceutical Design, Volume 21, Number 26, 2015, pp. 3760-3770(11). https://www.ingentaconnect.com/content/ben/cpd/2015/00000021/00000026/art00007 Panula, P. Histamine, histamine H3 receptor, and alcohol use disorder. British Journal of Pharmacology. 2019. https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14634 Zlomuzica, A., et al. 2016. Neuronal histamine and cognitive symptoms in Alzheimer's disease. Neuropharmacology. 106, 135e145. https://www.sciencedirect.com/science/article/pii/S0028390815001884?via%3Dihub Kim, H., et al. How stress triggers itch: a preliminary study of the mechanism of stress‐induced pruritus using fMRI. International Journal of DermatologyVolume 55, Issue 4. 2015. https://onlinelibrary.wiley.com/doi/abs/10.1111/ijd.12864 Prast, H., et al. 1996a. Histaminergic neurons facilitate social memory in rats. Brain Res. 734, 316–318. https://www.sciencedirect.com/science/article/pii/0006899396008864
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Heavy Metal Toxicity and Histamine Intolerance

How heavy metals may contribute to histamine intolerance symptoms What do heavy metals have to do with histamine intolerance? In our everyday lives, we’re exposed to a fair number of compounds that enter our body systems through the environment.In some cases, we’re quite aware of them, for example, in the case of pollution, herbicides, pesticides and even hormones in our meat.There are, however, other compounds we don't think about as often - and, we may not even know when we are being exposed to them, such as with heavy metals.In this article, I’ll dive into one of the most common metals you may be exposed to, where it may be hiding in your everyday life, what it could be doing to your health - particularly when you have histamine intolerance - and, most importantly, what you can do to reduce its impact on you. What are heavy metals? Before I discuss the specific heavy metal we'll focus on today, I want to first address the more general question of “what is a heavy metal?".Let me explain…Think back to high school science classes for a minute. Do you recall learning about the periodic table? Don’t worry, I’m not going to make you recite the periodic table and all of its elements, I just want you to recall what it contains. That’s right! All of the metals we have identified that can be obtained from our environment. Metals actually form a big part of our lives and, with the discovery of many of them, they have changed the way we can live, learn and improve how we go about doing things. One of the most precious heavy metals we have discovered is platinum - while some of the most useful are aluminum and cadmium, for example.Other heavy metals provide the body with important minerals we need to survive, for example, iron and zinc, while others are well-known for having serious and negative effects on the human body, for example, mercury and lead. The truth is, even though there are many metals that have been deemed safe - and even necessary - for our bodies, with high levels of exposure, they can still cause serious harm.Unfortunately, when you have histamine intolerance, it is possible that your exposure to heavy metals may be too high, and it could be contributing to your histamine intolerance symptoms. Now let’s get into one of the metals that has been associated with histamine intolerance: aluminum. Aluminum and histamine intolerance Aluminum is in everythingBecause of its low density and ability to withstand corrosion, aluminum has been incorporated into may aspects of our lives.Think about all the places you’d see aluminum being used in your direct environment. Have you pictured aluminum foil, cans, and food trays? What about door and window frames, cars, trucks, bicycles and spacecrafts?Did you know aluminum is also used in furniture, cooking utensils, deodorants, cosmetics, toothpaste, sun cream and medicines? It’s also in the food you eat, the water you drink, the air you break and the soil you may come into contact with (1). You can now begin to see how much aluminum you’re exposed to on a day to basis. Although the body is well-adapted at eliminating aluminum in the urine and feces, when you’re constantly being exposed to aluminum and your liver is unable to cope, there’s a risk of higher than typical levels remaining within your body. Research into the effects of aluminum and the effects it may have in humans, has not yielded any conclusive results, with data showing that exposure in the majority of the population is small. In these people, their bodies do eliminate aluminium at the appropriate levels, but what about when someone - like you - may not be eliminating it as needed. Let’s look at some of the research that suggests aluminum exposure may be more harmful in some. Allergies increase in those exposed to aluminum-containing treatments There are a handful of reports suggesting that medication that contains aluminum can increase the risk of allergy, particularly in those who are suffering from allergies to begin with. Studies show that dermatitis from aluminum-containing treatments worsens, and that these effects appear to be on the rise (2,3). It is well-known that aluminum induces an immune reaction, which stimulates mast cells where it promotes the release of histamines and other inflammatory mediators (4,5). One of the most recent studies done on the effects of aluminum on mast cell activation was performed on rats, where it was found that when these animals were exposure to aluminum in their food, there was a significant impact on mast cell activation and histamine release (6). That’s not all. This particular pathways induced irritable bowel-like symptoms in the rats, after which the authors concluded that it was highly likely that through mast cell activation in the gut, aluminum was able to induce IBS (6). Considering the strong link between IBS and histamine intolerance (58% of those with IBS have histamine intolerance to some degree), we can begin to see the link. If you have a higher than typical exposure to aluminium (or other heavy metals, for that matter), is it possible that it has induced your histamine intolerance and contributed to your digestive issues that are much like IBS? It’s highly possible. So, what do you do about it? How to reduce heavy metal levels for histamine intolerance Your first step in the process to reducing the impact that metals like aluminum have on your health is to get rid of as many of the factors in your environment that expose you to it (7). Stop using aluminum foil in your home and, in particular, never heat food wrapped in foil or foil containers. Where possible, replace aluminum lined pots and pans. Use aluminum-free cosmetics, toothpaste and deodorant. Ask your doctor whether any of your medications contain aluminum and, where possible request other alternatives. Check the ingredients in the products you use on a regular basis to determine their aluminum content. Avoid exposure to waste water, industrial steel areas, and tobacco smoking. Be sure to reduce your environmental exposure to other metals such as lead, cadmium, bismuth and mercury, as they too have been found to mediate mast cell release of histamines and other inflammatory compounds.  Natural ways to help your body to get rid of heavy metals involves Eating lots of organic, well washed fruit and vegetables instead of packaged foods. Focussing on adding a wide variety of low histamine fruit and vegetables to the diet, rich in nutrients that support the liver. Increase intake of dietary fiber to improve the movement of waste products from the body through stool. For dietary specifics, please download the free low histamine diet guide by clicking below   Get the FREE eBook   Overall, the best way to reduce the impact of aluminum and other heavy metals on your health is to minimize your exposure to it and to optimize your diet in order to best support a healthy body which can adequately detoxify. By dampening the impact  of environmental factors while prioritizing bodily health, this is one of the many ways you can focus on improving on your histamine intolerance and the process of healing!   References: Klotz, D., et al. The Health Effects of Aluminum Exposure. Dtsch Arztebl Int. 2017 Sep; 114(39): 653–659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651828/ Lund University. "Allergy treatments containing aluminum may cause new allergy, study suggests." ScienceDaily. ScienceDaily, 15 December 2010. https://www.sciencedaily.com/releases/2010/12/101214085545.htm Kutlu, A., et al. Could aluminum be a new hidden allergen in type 1 hypersensitivity reactions when used as a drug additive? Postepy Dermatol Alergol. 2016 Jun; 33(3): 243–245. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969423/ McKee A., et al. Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J Immunol. 2009 Oct 1; 183(7):4403-14. https://www.ncbi.nlm.nih.gov/pubmed/19734227/ Fang, X., & Xiang, Z. Roles and relevance of mast cells in infection and vaccination. J Biomed Res. 2016 Jul; 30(4): 253–263. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946316/ Esquerre, N., et al. Aluminum Ingestion Promotes Colorectal Hypersensitivity in Rodents. Cellular and Molecular Gastroenterology and Hepatology. 2019. 7(1):235-236. Exley, C. Human exposure to aluminium. Environ. Sci.: Processes Impacts. 2013. 15:1807-1816. https://pubs.rsc.org/en/content/articlehtml/2013/em/c3em00374d
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Histamine Intolerance and the COVID-19 Pandemic

Histamine intolerance and COVID-19 We’re living in a time of real uncertainty with the worldwide spread of COVID-19 (coronavirus) and anxiety levels are either high, or people are living in absolute denial about its impact. The most important thing is to remain calm and clear-headed in situations such as these, and listen to good quality, sound healthcare advice, based on evidence collected by scientists.   And, although my emails have been blowing up with requests to collaborate on coronavirus research projects or provide healthcare strategies to the public for boosting the immune system, I wanted to first take the time to give that information directly to the faithful readers of my own blog.  Especially considering that here, we deal with histamine intolerance as the focus. Many of you are histamine intolerant, many of you have a compromised immune system and many of you are already dealing with the symptoms of a chronic disorder. So, the fears surrounding this situation and the potential consequences, certainly aren't helping. If you have any concerns or worries about the implications of infection while living with histamine intolerance, I'm here to help you with as much information as I can.  It is, however, extremely important to note that, because this form of the coronavirus is classified as a new strain of virus, there is limited scientific evidence available on its precise mode of action and infection. That being said, what I discuss in the article below is based on what we know so far and the importance of protecting yourself  while managing your histamine intolerance. Coronavirus: known ways to protect yourself  First, I want to reiterate one important point... This is one of the most important things you can do Think back to your childhood for a minute. At school, it was common for bugs to be rapidly spread from one child to the next. It wasn’t long before children throughout the school were displaying the same symptoms.  Why? Let me explain. Children are always in contact with one another; if they’re not sharing their lunches, they’re using one another’s stationary, playing with toys that other children have been playing with, and generally getting down and dirty while going about their everyday lives.  Of course, young children don’t always consider washing their hands.  As an adult, we can equate these child-like behaviours to things we do every day. We work in close contact, we may still share stationary, desk space or equipment, we have lunch together and share utensils in communal kitchens or canteens, and we touch surfaces that have been touched by thousands of others as they go about their daily lives (think public transport, malls, stores). Do we wash our hands? Not nearly as often as we should.  That’s why the health authorities have really stressed this point in the media. You’ve likely heard it a million times before, and it’s important you hear it again: a seemingly simple act such as washing your hands can have a significant impact on the spread of germs; not only to others, but to yourself.  Just like good hygiene, keeping your distance from people is important. We don’t want to be touching unnecessarily; you never know who has or who hasn’t washed their hands! It has also been suggested that droplets in the air with mucus from an infected person may increase risk of infection to others - and droplets can be released through talking, laughing, sneezing, coughing.  Now that we've gotten that out of the way, back to histamine intolerance and COVID-19.... Histamine intolerance, COVID-19 and the immune system There are a number of factors to consider when we’re looking at the immune system in someone living with histamine intolerance: The branches of the immune system The current state of the immune system and inflammatory responses in someone with histamine intolerance of mast cell activation syndrome (MCAS) The release of inflammatory cytokines induced by both histamine intolerance and COVID-19 Firstly, let’s discuss the branches of the immune system, of which there are two.  We have a Th1 and Th2 branch, the former is the one we are born with, called the innate immune system, and the latter,  the one we acquire as a result of our environment and exposure to specific foreign invaders, is called the adaptive immune system.  The Th1 immune response plays a critical role in how the Th2 immune branch responds to viral infections.  Take measles, for example. It’s the response of the Th2 branch that provides us with lifelong protection against these types of contagious diseases. If you’ve had measles before, you won’t get it again because of the way your adaptive immune system built up protective mechanisms against it ever being able to cause a problem again.  Histamine actually regulates this branch of the immune system through various cells involved in its processes. The cells, such as T-cells, have histamine receptors on their surface, and they are also able to secrete histamines(1).  Information about COVID-19 and its effect on T-cells and other immune mechanisms is still being studied, but the most recent and similar outbreak of a coronavirus, namely that of the SARS-CoV in 2003, may offer some insight. It’s a complex series of mechanisms, but the basics of the severity of infection rely on the virus to be able to suppress or inhibit the immune response and low T-cell response because of it.  An interesting parallel between the SARS-CoV and COVID-19 is what happens in infected children, based on this T-cell idea. It appears that adolescents have a far higher immunity to the disease than adults. Children may be carriers of the disease, but currently, largely seem to display very mild symptoms or even none at all(2). One of the reasons scientists suspect this is the case is that children have a far higher T-cell immune response. Their T-cells may still be adapting to their environment, and so their immune system is able to ‘pick up’ the virus and contain it more readily than an adult, who may have more inactive T-cells because of an ageing immune system. This reduced capacity of the immune system to respond may leave an individual at greater risk of developing symptoms when infected(3). Another consideration is the simple response of the immune system to a viral infection. If some of the processes involved in the activation of these immune system branches are delayed, which may happen as a result of an infection such as that by the coronavirus, the virus is in a more favourable environment to be able to replicate(4).  A higher rate of replication induces hyperinflammatory conditions and there is a higher influx of inflammatory chemicals into the site of infection, namely the lungs in COVID-19. The ability of the virus to dampen a person’s response is closely associated with disease severity(4).  Secondly, we need to consider how histamine intolerance or mast cell activation syndrome (MCAS) influences the immune system and subsequent inflammatory responses.  When you’re living with histamine intolerance, your immune system is on high alert. With a highly active immune system comes more active mast cells.  Mast cells, as you well know, are a major source of histamines in the body; when we further look at higher histamine levels, we know that histamines can also trigger mast cells to release their contents, which amongst many other chemicals, includes specific inflammatory chemicals, called cytokines(5).  Now for the third point, and getting into the role of cytokines… A consideration for those with histamine intolerance and COVID-19 infection Histamines are considered potent inflammatory mediators and when the histamine pathways are stimulated, there is an amplification of inflammatory reactions and cytokine release at the sites where the histamines are most common; one of them being the tissues in the lungs(6,7).  Current information we have on what happens with COVID-19 is that it, too, has an effect on the body’s inflammatory response and, as a result, triggers the release of cytokines. One of the ways in which it is suspected that COVID-19 causes damage to the lung tissue is through this very mechanism, with high release of levels of inflammatory chemicals, including cytokines, within the lungs.  This is in no way intended to be alarmist, however, it is a valid concern for those living with active histamine intolerance or MCAS, and in particular, if you have the manifestations of your condition in the lungs, namely, asthma, or any breathing-related symptoms.  Having this information on hand also helps you in two main ways: You have a clear reason to take the advice of the health advisory boards and follow it as closely as possible, maintaining proper hygiene and social distancing/isolation.  Should you need to be tested for COVID-19 due to a suspected infection, know that you should make it clear on your intake/questionnaire that you are at a higher risk. Here are a number of ways you can clearly state this during assessment. Tell your healthcare provider or the nurse who is assessing you that you have: An inflammatory condition - use the words mast cell activation, histamine toxicity, or histamine disease to describe it rather than histamine intolerance in this case, as many doctors may be unfamiliar with the disorder.  Episodes of asthma A respiratory illness or condition There is also a lot you can do to continue to manage your body’s immune and inflammatory responses during this time: Stick to your low histamine diet as much as possible. Include healthy, anti-inflammatory foods into every meal. I've linked the histamine intolerance foods list for your reference. Continue with your current supplements. Order your new stock before you usually would as there may be delays in shipping due to high demand. I have also seen multiple supplements going 'out of stock' and websites putting purchasing caps on people to prevent supplement-hoarding. Keep in mind, everyone is concerned about their health right now - there is no need to panic and hoard every supplement out there, but simply to be sure you're stocked on the supplements you need for supporting your condition. Manage stress and anxiety. If you’re home-bound, take this time to relax, meditate, journal! Do anything you can to keep your mind calm and clear. There are plenty of free apps and channels to meditate, follow a yoga flow or do a home-workout. Now is the time to use these resources. Stay positive. Continue with hobbies, connect with loved ones over the airwaves and try to keep your spirits high. Check on your friends. Be sure everyone in your network is alright, as well. Some individuals may find the isolation very challenging.  Ask for help. Community is what comes together in times of crisis; ask friends or neighbours to assist with groceries if you have limited access to stores or online options. Do what you can to reduce your risk of infection. Wash your hands for a little longer, wash them more often than you would, and stay home where you can! If you do your part, there’s a much higher chance of there being faster containment, and a return to our day-to-day lives.  One last thing to remember is that, although now is the time everyone is worried about their health and social distancing is in place, we must also come together with our capacity to care for one another and provide support for those around us. Some people may find isolation mentally challenging, or not be ale to go to the grocery store for supplies at all. Our loved ones may be lonely and afraid. Call them, ask them if they need help, lend a hand in any way you can while still staying responsible and keeping yourself safe. We are all hoping this nightmare will be over soon. Stay safe! References: Ferstl, R., et al. Histamine regulation of innate and adaptive immunity. Front Biosci (Landmark Ed). 2012 Jan 1;17:40-53. https://www.ncbi.nlm.nih.gov/pubmed/22201731   Liu, W., et al. Detection of Covid-19 in Children in Early January 2020 in Wuhan, China. The New England Journal of Medicine. 2020. https://www.nejm.org/doi/full/10.1056/NEJMc2003717   Zhao, J., et al. T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice. Journal of Virology. 2010. 8(4): 9318–9325 https://jvi.asm.org/content/84/18/9318.short  Prompetchara, E., et al. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol DOI 10.12932/AP-200220-0772 https://apjai-journal.org/wp-content/uploads/2020/03/AP-200220-0772.pdf  Branco, A., et al. Role of Histamine in Modulating the Immune Response and Inflammation. Interplay between Hormones, the Immune System, and Metabolic Disorders. 2018. 9524075 https://www.hindawi.com/journals/mi/2018/9524075/  Dunford, P., et al. The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells The Journal of Immunology, vol. 176, no. 11, pp. 7062–7070, 2006. https://www.jimmunol.org/content/176/11/7062  Thangam, E., et al. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets. Front. Immunol., 13 August 2018. https://www.frontiersin.org/articles/10.3389/fimmu.2018.01873/full 
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Low Histamine Cauliflower and Pomegranate Salad Recipe

Mixing smokey and sweet to give your taste buds a tingle! Are you ready for a sweet and savoury combo that will knock your socks off? Well this low histamine cauliflower and pomegranate salad is about to punch you in the feet.This delicious smokey and crunchy salad pairs well with a piece of freshly cooked meat or, can be eaten on its own if you're in an all-salad mood. With the sweet, yet tart combo of the pomegranate seeds, cauliflower as a main ingredient might just become your new favourite food. That brings me to the health benefits of the ingredients in this delightful, summery salad. Remember, I always choose my ingredients very carefully so they're not only low in histamine, but prevent histamine release and promote total-body health and healing. Check out my foods list for a comprehensive guide to the best and worst foods for healing histamine intolerance! Get the FREE Food List Now, let's look further into what you'll be eating... Low Histamine Salad: Nutrition Info Cauliflower is a seriously low calorie food with only around 25 calories per cup, but don’t let that lead you to believe that it’s low in nutrients, too. As far as superfoods go (which, by the way, isn't exactly a real term we use as scientists) - well, cauliflower is about as close as it comes to achieving this status! (Or, anything from the Brassica family, really)Cauliflower is packed with fibre and vitamins, particularly vitamin C and vitamin K, which makes it an excellent choice as a staple in your low histamine diet. Research shows that vitamin C can help to stabilize mast cells and break down histamine.In fact, it’s one of the nutrients given to seamen who suffer from motion sickness, which typically involves a histamine response (that's SEA-men, to clarify). In addition to its function to help you to manage your histamine intolerance, cauliflower has been shown to be full of inflammation-fighting antioxidants, which can help to reduce the risk of disease, including cancer and heart disease. Another bonus about cauliflower (gosh, I feel like I'm in love with cauliflower) is its choline content. Choline is an important nutrient that is involved in DNA maintenance, it is important for the function of the nervous system and it has been found that those who have low levels of choline in their diet also have a higher risk of heart and liver disease, as well as neurological disorders like Alzheimer’s and other dementias. In general, cauliflower provides a great nutrient-rich alternative to gluten-containing grains, which you’ll want to avoid on your low histamine diet. Ok, I'll shut up about cauliflower now and (sadly) move onto something else.Wait, one more thing! Here's 3 other low histamine recipes with cauliflower: Cauliflower Low Histamine Hummus Recipe Low Histamine Cauliflower Rice Pudding Recipe Roasted Low Histamine Salad Recipe Ok I'm done now, promise.Another powerhouse ingredient in this salad is the pomegranate seeds. Many fruits cause symptoms in those with histamine intolerance; fortunately, pomegranate is not one of them. Lucky for you, this fruit, that contains so many beneficial properties that’s unrivalled by many other foods, has made its way onto your list of foods to enjoy. Not only do pomegranate seeds provide a wonderful pop of colour to your meals, they add a tangy sweetness will very few calories, a little bit of a crunch, and another source of that sought-after vitamin C.Along with it’s histamine-lowering properties, you can thank pomegranate seeds for their anti-inflammatory effects, blood pressure lowering properties, pain relieving capabilities, and anti-microbial action, all of which can further help you to manage your health and improve your quality of life. This really is a great tasting, healthy and satisfying salad that pairs well with many other dishes. If you’d like, add freshly cooked steak or chicken to make it a meal for the whole family! Low Histamine Cauliflower and Pomegranate Salad Recipe Makes 4-6 servingsCalories: 120 (Carbohydrate 15g; Protein: 4g; Fat: 6g)Ingredients: 2 heads cauliflower, broken up into medium sized florets 2 tbsps olive oil (more for serving - optional) 1 tsp ground turmeric 1 tsp ground coriander Pinch salt ¼ tsp freshly ground black pepper ¼ medium white onion, finely diced 2 tsp pure, raw honey or maple syrup ½ - ¾ cup fresh pomegranate seeds ½ cup fresh parsley, roughly chopped 1 cup cooked chickpeas (optional for those who have reintroduced and can tolerate legumes, as they contain other biogenic amines - if unsure, omit this ingredient) Instructions: Preheat the oven to 425 F. In a large bowl, toss the cauliflower florets with the oil, turmeric, coriander and salt and pepper until well coated. Move onto a lined baking tray and spread out into a single layer. Roast for 20 minutes, until the cauliflower begins to brown, turning once during the process. As the cauliflower is roasting, in a serving bowl, add the onion, pomegranate seeds, parsley and optional chickpeas set aside. Once the cauliflower is cooked, drizzle with the honey and set aside to cool. Once cooled, add it to the serving bowl with the other ingredients and serve immediately. Drizzle with a little olive oil if desired. Want more low histamine recipes like this? Check out my nutritionist-approved Low Histamine Cookbook with 110 delicious histamine intolerance recipes!  Get the Cookbook! Put your health in nature's hands. Anita Tee, Nutritional Scientist
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Histamine Intolerance, Estrogen and Hormonal Imbalances

Your hormones are there to tightly regulate many critical processes that take place in your body. When they’re doing their job, you have loads of energy, you’re fit and strong, you’re on the ball and you simply feel amazing every day.But, as someone who has histamine intolerance, do you even remember what feeling this way is like anymore?No?Well, one of the reasons is because those essential hormones, that are supposed to keep your body running like a well-oiled machine, have started to cause problems instead.The hormone estrogen and its dysregulation is the one we’re going to focus on today. The histamine estrogen connection Histamine intolerance (HIT), affects many more women(1) than it does men and it may be because estrogen is predominantly found in women. We say predominantly because men also require a certain level of estrogen to function. For the sake of ease of understanding, this article will address what typically happens in the female body when it comes to the interplay between estrogen and histamine. As a recap, estrogens are actually a group of hormones produced by the ovaries and they are important for sexual characteristics and reproductive development.While estrogens are normally under tight regulation during a woman’s reproductive years, we are seeing more and more dysregulation of this group of hormones in younger women. Symptoms of estrogen imbalance include: Irregular, heavy or painful periods Changes in bowel movements (diarrhea or constipation) Breast tenderness and other symptoms of PMS Acne Fatigue Irritability and anxiety Etc. Estrogen production can be affected by a number of factors; some of them, most commonly being blamed as a result of our modern day lifestyle and habits, include: Stress Exposure to toxins, chemicals and heavy metals Use of oral birth control Chronic illness and inflammation Diet Get the Low Histamine Diet But what does this have to do with HIT?From the symptoms related to estrogen imbalance listed above, it’s easy to see they can be very similar to symptoms of histamine intolerance; and that’s because of the close link between these two chemical messengers and how they affect one another. Histamine intolerance or her-stamine intolerance?Estrogen production surges at specific intervals throughout the month, and these surges are followed by lower levels of the hormone. This process relies heavily on the body’s ability to clear estrogen, in other words, break it down and render it inactive(2). If estrogen levels remain high, it continues to signal specific tissues to continue performing a function; but one that may no longer be required(2)!One of the many signalling pathways that estrogen uses is via the H1 receptor(2).And where do you know about the H1 receptor from? Histamine activation, of course! Histamine also uses the H1 receptor to activate a response. (If you need to brush up on the different histamine receptors and their associated functions - check out my ultimate guide to histamine intolerance)But here’s the catch: estrogen, when binding to the H1 receptor on mast cells, causes an increase in histamine release, particularly in the uterus and ovaries where it elicits its greatest response. That means, when estrogen is not cleared as it should be, more histamine is released, and histamine load increases(3). Mast cells also have sex hormone receptors, which means they can respond to signals directly from estrogen or progesterone. If you have higher than normal estrogen levels, mast cells are more readily activated, and histamine levels in the body rise(4,5). Then, you have the effects that histamines have on estrogen, that takes place at the same time.As more histamine is released into your system, estrogen production is stimulated, and it kicks off a vicious cycle of dysregulation of both chemical messengers(6). For this reason, many women experience a worsening of their symptoms around the time of ovulation and then again just before menstruation begins(7). There’s also the question as to how estrogen affects the DAO enzyme that histamine needs to be broken down. This link becomes more clear when we look at what happens during pregnancy. Have you ever heard that pregnant women have almost spontaneous resolution of immune disorder symptoms? It’s by no means a miracle, even if the baby is! This resolution has to do with the alterations in hormones necessary to maintain pregnancy in addition to the extremely high level of production of the DAO enzyme by the placenta(8). This last fact about DAO production by the placenta is quite interesting. Histamine has a stimulatory effect on tissues, including the embryo and uterus. Because of this, the placenta acts as a DAO-containing barrier or shield to prevent the effects that histamine may have on the maintenance of pregnancy and fetal growth and development(8). When considered together, both of these above-mentioned factors significantly reduce histamine load, which is why symptoms decrease in pregnant women(9). While it’s clear that estrogen has a role in histamine load and vice versa, the question still remains: what can you do about it? Balancing hormones to tackle histamine intolerance One change you can begin to make right now in how your body reacts to histamine is to look at your diet. To give your body a break, it's important to cut out as many histamine increasing or DAO-blocking foods. You can access a comprehensive list of both high and low histamine foods here. At the same time, you can begin your investigation into the role estrogen plays in your histamine intolerance. It’s worthwhile speaking to your doctor to obtain tests to determine your hormone levels, which includes estrogen, progesterone and testosterone.Be sure to take note of where you are in your menstrual cycle when you get your results, as this can give you a fair amount of information as to whether your hormone levels are appropriate for that time of the month or not. If you’re highly stressed, are taking hormone therapy or have any other reason to suspect that your estrogen levels may be linked to your histamine intolerance, a full hormone test (such as the DUTCH test) can help you to pinpoint where the irregularities may lie.Two other factors to consider when it comes to managing estrogen levels are: Your liver function. Your liver makes and secretes bile into the gallbladder, which is needed to bind estrogen during the process of elimination. If the liver is not producing enough bile, estrogen can be reabsorbed into your system and continue to produce effects. Additionally, if the liver is underperforming for any reason, it may be sluggish in breaking down estrogen in the first place, allowing higher levels to be recycled in the body. Fiber content in the diet When fiber intake is insufficient, there may be impaired elimination of the products of estrogen through bowel movements. Infrequent bowel action may not only indicate lower levels of fibre in the diet, but also why there may be an increase in estrogen activity. Working with a qualified healthcare professional who specializes in hormone activity is highly recommended, as is the right approach to testing your hormone levels.It takes the guesswork out of what is actually going on in your body and provides you with a much clearer plan of action on what to do next.For a free guide to histamine intolerance along with the latest histamine info and articles sent straight to your inbox, click below to join our free newsletter! Join the newsletter References: Jarisch R. (2015) Histamine Intolerance in Women. In: Jarisch R. (eds) Histamine Intolerance. Springer, Berlin, Heidelberg. https://link.springer.com/chapter/10.1007/978-3-642-55447-6_6 Bodis J., et al. The effect of histamine on progesterone and estradiol secretion of human granulosa cells in serum-free culture. Gynecol Endocrinol 1993;7:235–9. https://www.ncbi.nlm.nih.gov/pubmed/8147232 Kalogeromitros D., et al. Influence of the menstrual cycle on skin-prick test reactions to histamine, morphine and allergen. Clin Exp Allergy. 1995;25:461–6. https://www.ncbi.nlm.nih.gov/pubmed/7553250 Zierau, O., et al. Role of female sex hormones, estradiol and progesterone, in mast cell behavior. Front Immunol. 2012; 3: 169. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377947/ Zu, T., et al. Estrogen is an important mediator of mast cell activation in ovarian endometriomas. Reproduction. 2018. 155(1):73-83. https://rep.bioscientifica.com/view/journals/rep/155/1/REP-17-0457.xml Maintz, L., & Novak, N. Histamine and histamine intolerance. The American Journal of Clinical Nutrition. 2007. 85(5):1185-1196. https://www.ncbi.nlm.nih.gov/pubmed/17490952 Hamada, Y., et al. Effect of the menstrual cycle on serum diamine oxidase levels in healthy women. Clinical biochemistry. 2013. 46.1-2: 99-102. https://www.ncbi.nlm.nih.gov/pubmed/23099198 Maintz, L., et al. Effects of histamine and diamine oxidase activities on pregnancy: a critical review. Hum Reprod Update. 2008 Sep-Oct;14(5):485-95. https://www.ncbi.nlm.nih.gov/pubmed/18499706 Morel F, Surla A, Vignais PV. Purification of human placenta diamine oxidase. Biochem Biophys Res Commun 1992;187:178–86. https://www.ncbi.nlm.nih.gov/pubmed/1520298
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How GMO’s and Glyphosate Impact Histamine Intolerance

Here’s how changes in agricultural practices may have contributed to a rising incidence of histamine intolerance There’s no question that food can affect your tolerance to histamine. There is, however, a question about what exactly is in the food you eat that leads to a poorer tolerance of its amine content. Histamine and glyphosate: it’s not always the food itself Histamine, as you may very well already know, is called a biogenic amine. Basically, that simply means it’s a compound with one or more amine groups, which are chemical compounds that are formed as a result of amino acids being broken down.Other biogenic amines are cadaverine and putrescine, which are foul-smelling amines that are associated with the breakdown of tissue in living organisms. Think about the stench of fish as it stands out in the sun. This is, in part, due to the release of these two compounds. Now, what do they have to do with histamine?Well, in the body, if there are in increased levels, they compete with histamine for breakdown. While less well-researched, the detrimental effects of cadaverine and putrescine may be considered to be greater than those of histamine, as they can cause an acute state of life-threatening symptoms (1,2). If you’ve ever had food poisoning, in particular, having landed up in hospital with an extreme reaction to something you’ve eaten, you’ll know why. When even small amounts of cadaverine and putrescine are ingested, for example, if you were to go out to enjoy a seafood dish predominantly made up of shellfish, and just a portion of it was underdone, it can have serious consequences.Not only can it cause almost immediate anaphylaxis - a life-threatening allergic reaction - it can make you extremely and violently ill. Of course, increased histamine ingestion with fish can also bring about these types of symptoms.In this case, where the condition is called scombroid poisoning, it is associated with increased histamine concentrations in fleshy fish a result of mishandling and improperly following of the cold-chain of manufacture (3).There is another commonality shared between histamine, cadaverine and putrescine; these compounds all rely on the DAO enzyme to breakdown. When cadaverine and putrescine are present, DAO prioritizes their breakdown and, therefore, their presence in the body may inadvertently increase the levels and ill-effects of histamine by placing even higher demand on DAO and reducing its capacity to further control histamine (4,5,6). There’s even evidence to show that cadaverine and putrescine increase histamine’s toxic effects because they facilitate histamine’s transportation rate across the intestine and into the bloodstream. At this point, you may be wondering how your levels of cadaverine and putrescine increase. You may argue that you don’t eat fish very often, or that you’ve never had an allergic reaction to fish.Well, the answer may surprise you. Contributors of cadaverine and putrescine Both cadaverine and putrescine are found in high concentrations in fermented dairy, such as cheese, and high concentrations are also found in fermented sausages, vegetables and fish products (7). But there’s another source: GMO crops. GMO foods and histamine intolerance Genetic engineering has changed the face of agriculture, bringing about a sustainable method of increasing crop resilience to pests, and allowing for a higher yield and delivery of staple foods to populations. For years, there has been a debate about the safety of GMO crops in humans, and it still rages on without a clear indication of the outcome in sight.What we do know, however, is that GMO crops are more readily sprayed with a particular type of herbicide that contains a compound called glyphosate. When this weed-killer was first introduced, it not only killed the weeds, but every living plant it came into contact with.With the introduction of genetic engineering, scientists were able to change how particular genes within plants reacted to the glyphosate and alter them to be able to withstand it - and other pests, for that matter - while the glyphosate continued to kill unwanted species around the desired crops. With most of the corn and soy used for human consumption across the world now being GMO crops, it is safe to say that these raw ingredients and the products made from them, may very well be contaminated with glyphosate. Non-GMO crops are also frequently sprayed with this herbicide at the time of harvest, to dry them out faster. Wheat, barley, nuts, peas and oats are some of those on the list. Even organic produce can be contaminated through the environment, and products made from plant materials may contain traces of it. GMOs, glyphosate and histamine symptoms Research published by the Scientific Reports journal in 2016 showed that GMO crops sprayed with glyphosate-containing herbicides contained higher levels of putrescine and cadaverine, in addition to higher amounts of each of their precursors (8). That being said, if we consider the way putrescine and cadaverine affect the body’s ability to manage histamine, GMO and glyphosate-contamination may be a significant area of histamine toxicity to consider in treatment. More recently, both putrescine and cadaverine have also been found to have direct implications on gut health.These compounds have shown to elicit profound and detrimental toxic effects on the intestinal cells, causing the death of the cells themselves. Histamine has a similar response, where it has been found to cause programmed cell suicide, or apoptosis, within intestinal cells, so there’s little wonder why this, along with another biogenic amine called tyramine, carry the potential to be the most toxic of all dietary amines (9). It now becomes clear that we need to consider the presence of all biogenic amines in foods and their contribution to histamine intolerance, in order to best understand and control histamine symptoms. How can I begin to reduce histamine symptoms? Following a low-histamine diet is only one way to reduce the symptoms you’re experiencing from suspected histamine intolerance. If you suspect histamine intolerance but haven't already begun a low histamine diet, it's essential to start this now. Start by following the foods list and guidelines in the free e-Book below. Start the Low Histamine Diet Along with dietary measures and controlling histamine input, it's also possible to enhance histamine breakdown within the body through the histamine-degrading enzyme, DAO.To maximize the effect of DAO and prevent an increased demand on its production, eating organic, non-GMO foods is also advised, as this can reduce the exposure to other biogenic amines, such as cadaverine and putrescine, which take precedence over histamine when it comes to breakdown by DAO. I've written an article on how to increase DAO enzymes naturally, which you can also read for more tips on upping histamine degradation.Additionally, because raw foods and other - even organic - crops may be contaminated by these compounds, foods should be eaten when they are at their maximum freshness, frozen immediately from fresh, or boiled and eaten immediately to reduce their biogenic amine content. Histamine intolerance is a complex condition with a number of contributing issues that may be underlying its development.And, although often forgotten, one of those underlying factors that needs to be considered is the contribution of changes in agricultural practice.Are you part of the population that may be reacting to these GMO foods and the contamination of glyphosate? It’s definitely worth investigating and taking action against it.Life's too short to let symptoms control you.Your histamine intolerance expert,Anita Tee, MSc   References: Del Rio, B., et al. The biogenic amines putrescine and cadaverine show in vitro cytotoxicity at concentrations that can be found in foods. Scientific Reports volume 9, Article number: 120 (2019). Ladero, V. et al. Biogenic amines content in Spanish and French natural ciders: Application of qPCR for quantitative detection of biogenic amine-producers. Food Microbiol. 28, 554–561 (2011). Hungerford, J. Scombroid poisoning: a review. Toxicon. 2010 Aug 15;56(2):231-43. Sahcez-Perez, S., et al. Biogenic Amines in Plant-Origin Foods: Are they Frequently Underestimated in Low-Histamine Diets? Foods. 2018 Dec; 7(12): 205. Jarisch R., Wantke F., Raithel M., Hemmer W. Histamine and biogenic amines. In: Jarisch R., editor. Histamine Intolerance. Histamine and Seasickness. Springer; Stuttgart, Germany: 2014. pp. 3–44. EFSA Panel on Biological Hazards (BIOHAZ) Scientific opinion on risk based control of biogenic amines formation in fermented foods. EFSA J. 2011;9:2393. European Food Safety Authority (EFSA). Scientific opinion on risk based control of biogenic amine formation in fermented foods. Panel on Biological Hazards (BIOHAZ). EFSA J. 9, 2393 (2011). Mesnage, R., et al. An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism disturbances caused by the transformation process. Scientific Reports volume 6, Article number: 37855 (2016). Linares, D. M. et al. Comparative analysis of the in vitro cytotoxicity of the dietary biogenic amines tyramine and histamine. Food Chem. 197, 658–663 (2016). Get Your FREE eBook
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Is Histamine Intolerance Genetic? DAO, HNMT, MTHFR and Other Important Genes

Is histamine intolerance in your genes? Your genes dictate who you are, and this is true for what happens both from a physical and a biological perspective!  Think about your eye and hair color. You weren’t randomly assigned to be born with green eyes and blonde hair, for example. Your carefully constructed genetic code allocated those specific traits to you, long before you were even conceived. In terms of biological genes, they are also responsible for your body shape, your likes and dislikes, your personality, and a whole lot of other things about you that make you, you.   Genes are also in control of many aspects of your health. Our genes can provide us with either protective aspects against certain diseases and conditions, or they can leave us more at risk.  When it comes to histamine intolerance (HIT), there are a number of genes that have been found to increase the risk of developing this condition.  Common genes that affect histamine intolerance: DAO, HNMT, MTHFR, MAO and HDC Without getting into too much of the science behind genes, there’s a little bit about them you need to know to understand why a genetic factor can be the cause of your symptoms of HIT.  Each gene is made up of a number of different codes. These codes tell the body to use specific nutrients to make enzymes. Enzymes are what make the entire body functions as it should, where these little compounds tell each cell what it needs to do.  Some genes have been put together with the wrong code, where it’s possible that a ‘typo’ crept in when your DNA was being made, or, you inherited the typo from one of your parents. Depending on how much of the code is wrong, the capacity of the enzyme which it instructs will be reduced, and so the enzyme simply doesn’t work at 100% of its true efficiency.  There are five common genetic changes that can increase your risk of histamine toxicity.  1. DAO - AOC1 Diamine oxidase (DAO) is an enzyme that the body uses to break down histamine. When there is too little of this enzyme produced, histamine levels within your system increase.  DAO is the primary enzyme that you need for histamine to break down, particularly when it comes to histamine in the gut. Because there is a chance of high histamine influx into the digestive system, both from food and that which is produced by gut bacteria, DAO really needs to be on point. When it’s not, and the gene that codes for its production is not working effectively, symptoms of histamine intolerance can arise(1,2).  When it’s a DAO deficiency that’s the cause of histamine intolerance, it’s referred to as a primary DAO insufficiency.  DAO supplements are available, which work very well when it comes to helping to break down histamine in the gut. The supplements, however, don’t add to the body’s overall capacity to produce DAO, making them a symptom-relieving option rather than being able to fix the root cause.  2. HNMT - C939T Another enzyme the body uses to break down intracellular histamine that is made or released elsewhere in the body is called histamine N-methyltransferase (HNMT). It is particularly active in the central nervous system, which is made up of the brain and the spinal cord(3). When there is insufficient HNMT made due to a genetic predisposition, there may be an increase in the symptoms of histamine intolerance associated with activation of the receptors in the brain, such as heightened anxiety, mood swings, and even Parkinson’s Disease(4,5,6).  3. MAO - MAO Monoamine oxidase (MAO) is yet another enzyme that helps to degrade biogenic amines such as tyramine, histamine and catecholamines. While it’s not the primary function of MAO to degrade histamine, too little of this enzyme can still impact histamine levels. Symptoms may be even more severe when there is a change in the gene that dictates the production of MAO, as levels of the other biogenic amines rise, too(7).  4. MTHFR - A1298 It is believed that around 50% of people have the MTHFR genetic mutation. This enzyme, called methylenetetrahydrofolate reductase (MTHFR), is an important one involved in the folic acid cycle. It’s a critical step in converting folic acid into another essential compound that is needed for a process called methylation.  Methylation is one of the pathways the body uses for detoxification, energy production, repair and inflammatory responses, and it also helps to reduce the body’s histamine levels. Methylation status can seriously impact histamine levels, where a decrease in the ability to methylate with this gene mutation can cause mast cells to release more histamine into the body(8,9). There is a way to skirt around this gene and its impact on methylation. Taking a methylated folic acid supplement for example, or increasing your choline intake, can help to improve methylation capacity and influence the processes needed for histamine balance(10,11,12).  5. Histidine decarboxylase - HDC Histidine decarboxylase (HDC) dictates how easily the body can make histamine from the ingested amino acid histidine. When there is a mutation in this gene, histamine levels may rise. Research shows that those who have changes in this gene are more prone to developing allergies and a runny nose as a result(13,14).  Histamine intolerance and genetics: the bottom line What is important to realize is that, while you may be a carrier of some of these genes, they don’t always mean for certainty that a condition will develop. The ‘activation’ of a specific gene can cause symptoms to develop, however, should these factors that influence the gene be managed, and the triggers of that gene be moderated, the condition may be well managed.  This concept is certainly applicable to histamine intolerance. Even if you have a reduced capacity to produce DAO because of a genetic predisposition, for example, decreasing your intake of foods that further inhibit DAO production may help to improve symptoms of HIT. Supporting the body and its genetic processes can be the reason you are able to fully manage your condition with few, or no symptoms related to it.  For this reason, a histamine reduced diet is one of the best ways to quickly decrease the symptoms of histamine intolerance as it significantly reduces the load that histamine may be having on your body. For a detailed list of foods to eat and avoid, as well as more information on relieving histamine intolerance symptoms, click below to get my free eBook which is the ultimate guide to histamine intolerance!   Get the FREE eBook References: Petersen J, Raithel M, Schwelberger HG. Characterisation of functional polymorphisms of the human diamine oxidase gene. Inflamm Res  2005;54(suppl):S58–9. https://www.ncbi.nlm.nih.gov/pubmed/15928835  Maintz, L. et al. (2011). Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities. Allergy, 66(7), 893-902. https://www.ncbi.nlm.nih.gov/pubmed/21488903   Schwartz, J , et al. Histaminergic transmission in the mammalian brain. 1991. Physiol. Rev. , 71, 1–51. https://www.physiology.org/doi/full/10.1152/physrev.1991.71.1.1?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed    Heidari, A., et al. Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability. 2015. Human Molecular Genetics. 24(20):5697-5710. https://academic.oup.com/hmg/article/24/20/5697/556613   Jiménez-Jiménez, F., et al. Thr105Ile (rs11558538) polymorphism in the histamine N-methyltransferase (HNMT) gene and risk for Parkinson disease. A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2016 Jul; 95(27): e4147. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058861/   Agúndez, J., et al. Nonsynonymous polymorphisms of histamine-metabolising enzymes in patients with Parkinson's disease. Neuromolecular Med. 2008;10(1):10-6. Epub 2007 Nov 6. https://www.ncbi.nlm.nih.gov/pubmed/17985251/  Maršavelski, A., & Vianello, R. What a Difference a Methyl Group Makes: The Selectivity of Monoamine Oxidase B Towards Histamine and N‐Methylhistamine. 2017. Chemistry: A European Journal. 23(12). https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201605430   Haenisch, B., Nöthen, M. M., & Molderings, G. J. (2012). Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics. Immunology, 137(3), 197–205. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2567.2012.03627.x   Fryar-Williams, S. Fundamental Role of Methylenetetrahydrofolate Reductase 677 C → T Genotype and Flavin Compounds in Biochemical Phenotypes for Schizophrenia and Schizoaffective Psychosis. 2016. Front. Psychiatry. https://www.frontiersin.org/articles/10.3389/fpsyt.2016.00172/full#B60    Chmurzynska, A., et al. Associations between folate and choline intake, homocysteine metabolism, and genetic polymorphism of MTHFR, BHMT and PEMT in healthy pregnant Polish women. Nutrition & Dietetics. 2019. https://onlinelibrary.wiley.com/doi/abs/10.1111/1747-0080.12549   Chew, T., et al. Folate Intake, Mthfr Genotype, and Sex Modulate Choline Metabolism in Mice. 2011. The Journal of Nutrition. 141(8): 1475-1481. https://academic.oup.com/jn/article/141/8/1475/4630515   Shin, W., et al. Choline Intake Exceeding Current Dietary Recommendations Preserves Markers of Cellular Methylation in a Genetic Subgroup of Folate-Compromised Men. J Nutr. 2010 May; 140(5): 975–980. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855263/   Garcia-Martin, E., et al., Histamine pharmacogenomics. Pharmacogenomics, 2009. 10(5): 867-83. https://www.ncbi.nlm.nih.gov/pubmed/19450133   Gervasini, G., et al., Variability of the L-Histidine decarboxylase gene in allergic rhinitis. 2010. Allergy. 65(12): p. 1576-84. https://www.ncbi.nlm.nih.gov/pubmed/20608921 
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Included within the Low Histamine Diet guide