What You Think Is A Food Allergy May Be A Histamine Intolerance
It is common for individuals who know they are reacting to particular foods to show negative food allergy results on testing. Frequently, these people are responding to biogenic amines such as histamine in their food. Histamine is normal and necessary in small amounts in the body, but a disequilibrium of histamine can exist if there is too much histamine made by the body, introduced into the body or the bodies capacity to degrade histamine is diminished. We are not meant to have excess histamine around. As soon as its job is done it is usually quickly metabolized. Problems come up when that process is not working well and histamine is continuing to be delivered in food or generated in or by the body.
The symptoms can be both acute or chronic and they can look very similar to an IgE-mediated allergic response. The more common immediate symptoms are:
- Digestive Tract: food intolerance, nausea, abdominal pain, diarrhea, bloating
- Lungs: Asthma like wheezing, shortness of breath,
- Heart: raised blood pressure, palpitations
- Head, Brain, CNS: headache, migraine, anxiety, feelings of panic, confusion, depression, temperature sensitivity
- Skin: itchy skin, hives, flushing, rashes
These are the most common signs and symptoms seen with histamine intolerance that is diet and gut related. For additional signs and symptoms check out the article called Mast Cell Activation and Histamine Intolerance.
In this article we will examine:
- What histamine is
- The difference in food allergies, food sensitivties and food intolerance (in this case histamine intolerance)
- Foods with high histamine and why there are so many food lists that are in conflict on the internet
- Comparing histamine intolerance to food allergies
- How to lower histamine through multiple avenues
- Low-histamine diet
- Proper handling of food
- Diamine oxidase (DAO) Enzyme
- Stabilizing mast cells,
- Decreasing histamine producing bacteria that live in the gut
- Removing drugs and supplements that are known to block diamine oxidase
This article will focus on histamine, although foods that we call "high histamine containing foods" could better be called "high biogenic amine containing foods" due to other amines also found in food which can often also cause reactions. We have paid a lot of attention to histamine as it has often appeared to be the culprit, but other amines in food can cause symptoms and we need to keep this in mind. A food can be low in histamine but high in another amine such as putrescine, tyramine, spermidine, or cadaverine. It appears many of them may have similar affects when in excess and often more than one is high. Currently, it is thought that most serious food poisoning due to biogenic amines are caused by histamine and tyramine. Histamine is the most common amine to be linked to health issues.
Intake of low amounts of biogenic amines normally does not have harmful effects in healthy people and they are known to be in a variety of raw foods in small amounts such as meat, fish, milk and fruits as well as some vegetables. However, when the amount in our food is too high and our enzymatic detoxification ability is inhibited or overtaxed, biogenic amines such as histamine cause symptoms. Histamine is a common culprit or at least noticed amine that has caused a variety of minor to debilitating health effects. I find when people have symptoms that come and go that seem to have no known cause after batteries of testing, and the symptoms appear to be reactions to high histamine foods, histamine intolerance is often part of the picture. Histamine reactions from food can have immediate reactions or appear as chronic symptoms if the foods are ingested on a continual basis.
Food Allergies, Food Sensitivities and Food Intolerance
Food allergies are categorized as an immunlogic hypersensiivity that is IgE mediated. Food sensitivities are categorized as immunolgic delayed reaction to food that is IgG and IgA mediated. The last category is Food intolerance and although many would categorize it as a non-immunolgic reaction to food, I don't think this is entirely true. We will take a quick peak at IgE, IgA, and IgG food reactions before looking at histamine intolerance.
IgE-Mediated Food Allergies Create High Histamine Too
IgE or Immunoglobulin E is an immediate response to a foreign substance that has entered the body. Sometimes these are called a Type 1 Hypersensitivity. Other family members may also have the same allergies. IgE mediated food allergies are consistent. The allergic individual reacts every time the food is eaten. The symptoms also occur quickly after the food is eaten. Anyone with an IgE-mediated food allergy will know the foods that they need to stay away from. These foods can trigger anaphylaxis which is a very intense and potentially devastating reaction. Folks who have severe IgE-mediated reactions usually keep epi pens with them. These are immediate and severe reactions to a particular food and there is massive release of histamine as well as other inflammatory mediators during this type of reaction. This is not related to histamine in the food, it is a reaction to a constituent in the food that the body believes is a toxin. Histamine intolerance is usually not so severe as is IgE mediated responses, although we will discuss a situation when histamine intolerance can become dangerous. IgE-mediated reations can be tested for in a lab or physicians office and usually is undertaken with skin prick or patch testing and blood tests. The tests are not perfect. False positives are common. Sometimes a person responds positive to a food tested but when they eat it the food does not incite a reaction and the person eats it on a regular basis. However, false negatives are uncommon. If the food tested is negative, IgE mediated allergy to that food is very unlikely. When someone suspects IgE-mediated food allergies but the testing is negative, the next likely question to ask is if the foods causing a reaction are not due to allergies are these reactions due to histamine intolerance?
When someone has an IgE reaction to a food, it is best to stay away from that food, although there are practitioners that assist people in regaining more normal immunologic reactions to allergens to help the individual tolerate accidental exposure.
Symptoms of IgE reaction to food would include:
- Swelling and inflammation
- Hives or rash
- Itchy skin
- Itchy throat, mouth and tight throat
- Difficulty breathing
- Anaphylactic shock - servere cases
IgA and IgG mediated Food Sensitivities
IgA and IgG mediated reactions are considered food sensitivities while IgE is a food allergy. These are sometimes called a Type 2 Hypersensitivities. IgA-mediated or IgA Immunogobulin A food sensitivities generally take place in a 2-6 day period and IgA antibodies are 6% of the serum antibodies. IgG or Immunoglobulin G is a reaction that takes place in a period of 2-20 days and IgG makes up 80% of the serum antibodies. These reactions are delayed, subtler and last longer than IgE reactions which are about .002% of the serum antibodies. Due to the symptoms appearing a couple days or longer after the food is eaten, connecting the reaction to the food can be difficult. The release of the IgA and IgG antibodies create an inflammatory process that can cause a variety of symptoms in the body. Similar to IgE reactions, This is another case where the body does not see the food constituent or constituents it is reacting to as being friendly and thinks they are to be attacked. Some people don't realize their inflammation is related to foods they are eating. This can be tested for, and since it is hard to pin point the foods causing reactions testing can be the best way to find an IgG reaction, although the tests are not always as accurate as we would like. IgG testing can be done with a simple finger stick to collect blood. Elmination diets and challange tests can also be helpful to find food reactions such as to histamine, other amines, sulfite reactions etc. Eliminating food sensitivities as a group can often improve a variety of illnesses that an individual has had trouble with for years. I won't bother to list the possible symptoms as they are quite varied and not what this article is about.
When What Looks Like A Food Allergy Is Really A Diet Related Histamine Intolerance
There are multiple types of food intolerances but we will focus on histamine intolerance. Although common, this has been an under-appreciated and poorly understood food intolerance. There is disagreement about the types of foods that contain high histamine as well as a lack of understanding the key issue. In this article we will examine histamine intolerance and its relationship to food as well as touch upon other reasons beyond diet for high histamine in the gut and look at the main culprit for the reaction which is low diamine oxidase enzyme. This is a topic with many twists and turns and therefore this is more of an introduction to the topic and a more in-depth two part article is available when you finish this one.
Part II: Histamine Intolerance Solutions
Digestive Tract Histamine Is From Multiple Sources
There can be excess digestive tract histamine reaction from either high histamine foods or some foods can cause the body to make histamine. To make matters even more murky, some gut bacteria can change the amino acid in the food called histidine into histamine or cause irritation to the gut wall causing release of histamine. These are the food/digestion related causes of histamine known.
- Food contains high histamine from bacterial alteration of histadine to histamine in the food
- Some Foods stimulate the body to make histamine
- Bacteria in the gut convert the amino acid histadine from incoming food protein into histamine
- Bacteria in the gut cause release of histamine by the body in response to gut irritation and damage they cause
- Toxins in the gut can cause release of histamine by the body in response to gut irritation and damage from the toxins
- Foods the person is otherwise sensitive to such as foods with gluten, dairy or other foods that commonly cause inflammation can be a source of intestinal irritation and damage causing hitamine release
- Dysbiosis, small intestinal bacterial overgrowth or fungal overgrowth or any number of pathogens can cause gut irritation and damage inducing release of histamine
- Other physical stress or mental/emotional stress can cause mast cell release of histamine adding to the histamine load.
- Low diamine oxidase can cause increased histamine - this is one of the main issues often
What Is Histamine And What Causes High Histamine in Food
Histamine is a biogenic amine that is either ingested or is made in the body by mast cells (and to a less degree in some other cells) or gut bacteria. Amines in food result from protein breaking down into metabolites of amino acids. this happens from the food getting older without refrigeration to retard bacterial growth (aging the food), processing the food such as in processed meats or fermented vegetables or letting cooked food sit unrefrigerated on the counter. Amines are also found in larger amounts in overcooked meats. Browning, grilling, and charring all increase the amine content in meats. In fruits the amine content can rise when the fruit is extra ripe or past ripening. You might not want to put that over ripe banana in banana bread any more as those histamines won't be destroyed by baking.
Foods known to be high in histamine
Histamine is variable in foods and hard to quantify. This is because all amines in general are formed by bacterial degradation. Histamine is formed by bacteria activity that degrades histadine (an amino acid) to histamine (an amine). Meats, aged cheese and spoiled or extra ripe fruits are the most likely to have amines, but any food can contain them. The list of high histamine foods below are based on the fact that these foods can have high histamine. If they are fresh such as a freshly killed animal, or freshly caught fish, or a fruit that is not overly ripe or attacked by insects and bacteria a histamine intolerant person will usually be fine eating them. Someone who reacts to canned tuna will often find that a freshly caught and cooked tuna is no problem.
Cheese, beer and wine can have a highly variable content of amines including histamine depending on their fermentation process. A barely ripe fruit will have much less histamine than an overly ripe fruit. (avocado and tomato fit in here as a fruit)
You will see people list various fruits such as strawberries, avocados and banana on high histamine lists. Indeed any of these that are overly ripe or past ripe will have higher histamine, although nothing like an aged meat or cheese, but if they are just ripe with no blemishes, dark spots or damage, they will not have as much histamine content. This is why some people claim they are low histamine and others claim they are high. Strawberries are also thought by some to cause your body to produce histamine. Not everyone agrees and the reason could be differing reactions in various individuals. This needs to be studied.
Foods That Are Considered High Histamine (or other amines)
- Any meat, fish, chicken or other high animal protein that is not fresh
- Cured meat such as salami, prosciutto etc.
- Aged beef
- Some smoked meats
- Aged cheese
- Fermented vegetables such as kimchi, sauerkraut, sour pickles
- Fish sauce
- Shrimp paste
- Fish paste
- Fermented anchovies
- Soy sauce
- Red pepper paste
- Soybean paste
- Champagne is sometimes quite high
Any food that has been fermented or cultured is suspect as having high histamine.
Focus on FRESH FOODS!
Some Foods May Cause The Body to Release Histamine
These foods are thought to cause the body to release histamine, however research is needed. Some of these could have high histamine content if bacteria is growing in or on them.
- Egg white
- Chemicals in the diet
- monosodium glutamate
- food dyes
- food flavorings
- food preservatives
Watch out for alcohol And Yeast
Alcohol makes acetaladehyde. Both alcohol and acetalaldehyde liberate histamine from mast cells and inhibit the diamine oxidase (DAO) enzyme that degrades histamine. By the way the yeast called Candida also makes acteylaldehyde, so it too can liberate histamine and inhibit DAO theoretically.
With ingestion of alcohol, histamine has a good role to play as the body uses it for protection from alcohol-induced stomach and intestinal damage as well as bronchial asthma and flushing (in Asian studies). However, alcohol increases histamine and in the histamine intolerant adds to their histamine load.
The most common solution histamine intolerant people come up with is to avoid the foods that make them react. Indeed, histamine free diets are shown to help alleviate many symptoms, but some people end up with only a handful of foods they are eating. Most foods contain some amount of histamine, but there are those known to be very high in histamine. These foods are indeed good ones to temporarily remove from the diet, but this is usually not a permanent solution.
Rather than just removing foods, how about making sure all food that is eaten is fresh. Additionally, we can add foods to the meals that are known to inhibit histamine release from mast cells. Studies have shown Watercress inhibits 60% of histamine release, while Moringa inhibits 72%. Many other foods are known for stabilizing mast cells and decreasing histamine release.
Protective Foods That Decrease Histamine Release From Mast Cells
- Fish oil
- Mung bean sprouts (48 hours of sprout growth)
There are many more herbs and supplements that stabilize mast cells and prevent histamine release as listed in the article Mast Cell Activation and Histamine Intolerance.
The Enzyme Diamine Oxidase (DAO)
Diamine Oxidase or DAO is an enzyme that is made in the cells of the small intestine and the upper large intestine. Diamine oxidase is created in the intestinal wall cells and released into the the gastrointestinal tract to rapidly remove histamine in the intestine. Diamine oxidase is the enzyme that scavenges histamine that is outside of cells while the enzyme histamine-N-methyltransferase (HNMT) is the enzyme that removes histamine inside of cells in conjunction with S-adenosylmethionine (SAM-e) forming N-methylhistamine. If histamine makes it past the DAO, and gets into the intestinal wall cells, HNMT inside the cells is there to degrade histamine. This prevents excess histamine from getting into the blood stream. However, when it is high or one or both of these enzymes are not in high enough concentration, histamine does get by them and into the blood stream where it can roam around the body. Since the histamine in the gut is outside of cells, DAO is the main enzyme responsible for metabolising histamine in the intestinal tract. Anyone with low DAO is at risk of intolerance or outright toxicity from histamine.
Genetic induced low DAO: The number one factor for histamine intolerance has been found to be impaired enzymatic degradation of histamine caused by either genetic or acquired impairment in DAO enzyme production. Both DAO and HNMT can have genetic variants that limit their activity. Some people are low in DAO due to polymorphisms of a single nucleotide in the gene that encodes this enzyme (AOC1 on chromosome 7).
Non genetic induced low DAO: Other people have what is usually a temporary lack of DAO due to inflammatory or degenerative bowel diseases that can have temporary DAO deficiency while the illness is active. Anything that may alter the enterocytes (intestinal cells) may decrease DAO production. This means anything that causes intestinal inflammation is a possible factor in histamine intolerance. Excess histamine does not stay in the vicinity of the gut. If DAO is not sufficient to degrade it, the histamine goes through the intestinal wall into the cell and if HNMT and DAO (there is some DAO in the cells also as this is where it is made) is not sufficient to degrade it in the cell, the excess histamine can cross over into the blood stream and moves around the body causing trouble. This is why symptoms show up all over the body in people with histamine intolerance. Additionally, if a person is intolerant to histamine in the diet and has hay fever too, they will be dealing with a double edged sword. Lowering the gut histamine can take a load off of this person and is easier to control than pollen. This can help such an individual often.
Some Drugs Are known to block or inhibit DAO production
- Acetylcysteine (not a drug, a supplement)
- Clavulanic acid
- Pimagedine (AKA aminoguanidine)
A more extensive drug list can be found in the article "Diet, Gut Bacteria And Histamine Intolerance" article where both drugs that block DAO production and drugs that increase histamine for all reasons are listed. This article is almost finished, look for it soon.
The drug diphenhydramine has been shown to increase DAO activity.
Theoretically a lack of Vitamin C, Vitamin B-6, zinc or copper could cause a decrease in DAO as they are cofactors needed for DAO to do its job. Indeed the use of vitamin C an vitamin b-6 have been shown to increase DAO activity.
One study in healthy women showed a variety of nutrients supported DAO enzyme levels. These include:
- long-chain fatty acids, saturated fatty acids, and monounsaturated fatty acids
- saturation fats
- Vitamin B12
You Can Replace DAO
Luckily if an individual has genetics that decreases the amount of DAO made or if a person has other reasons for insufficient DAO it can be replaced with DAO supplements. Any companies DAO enzyme should work. I usually suggest a product by Seeking Health called Histamine Block to my clients.
The DAO products are all porcine or pig derived from kidneys, so vegans will not have an option for replacement unless they are willing to use what is available on the market currently. In this situation focusing on stabilizing mast cells and decreasing the bodies creation of histamine as well as decreasing bacterial induced histamine, eating fresh foods and avoiding higher histamine foods would be advised as the main options.
Decrease The Bacteria Making Histamine - Use Low Histamine Flora
We know that both pathogenic as well as commensal bacteria can make L-histidine decarboxylase (HDC) which is what the bacteria in food as well as in our gut use to turn histadine into histamine. Additionally, pathogenic bacteria and excessive growth of some commensal bacteria can irritate and damage the gut causing histamine release. If there are pathogenic bacteria found on testing in an individuals gut, they need to be attended to. The same with out of control commensal bacteria (these bacteria are considered normal and friendly when not in excess and abnormal if they are in excess). When commensal bacteria are out of control and they are known to make HDC, I suggest my clients use non HDC making bacteria replacement to help to control them before using antimicrobial herbs and supplements. The same company that makes Histamine Block provides such a product called Probiota Histaminx. If this does not take care of them, a more direct approach to the commensal bacteria needs to be undertaken.
What We Learned
We learned that histamine is made from the amino acid histadine and is created by bacteria in food that is not fresh. Some small amount of histamine can normally be found in food, but when food histamine is high it is due to bacterial activation in old or mishandled food OR it might be a cultured or fermented food where bacteria were used to alter the food into an aged cheese, a preserved meat, or soured vegetable.
Histamine can also be made in the body by bacteria that live in our gut. They can make histamine from histadine in the food eaten or if the bacteria is not completely friendly it might irritate the gut wall and cause release of histamine from mast cells. Histamine can also be released into the gut from other toxins or irritants. Intense acute stress or chronic stress of any kind may release histamine from mast cells in the gut.
Some people have genetic variants that keep them from making enough DAO.
Some people have acquired histamine intolerance that may be transient. This may be due to using DAO blocking drugs, or may be due to intestinal inflammation or damage from toxins or disease.
When there is not enough DAO, histamine in the gut is taken up into the bloodstream and increased plasma concentrations of histamine can cause symptoms elsewhere.
To lower our histamine burden we can eat fresh foods or properly prepared and preserved foods. We can also make sure we have adequate nutrients to make and use DAO. Supplements can be used stabilize mast cells and decrease histamine release and DAO enzyme can be ingested as a supplement. Additionally, we can use low histamine producing bacteria as flora replacement to compete for space in the colon with the bacteria that are making histamine.
If you want to know more about histamine intolerance and how diet and gut bacteria are involved as well as additional causes check out the two part article on histamine Part I: Histamine Intolerance Causes, Symptoms and Diagnosis and Part II: Histamine Intolerance Solutions.