This page is all about solutions to histamine intolerance. If you want to know more about what histamine intolerance is and what the causes are, please read the first part of this article called Histamine Intolerance Causes, Symptoms and Diagnosis. In that article we covered the following basic ideas.
- 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 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.
- Eating a low histamine diet can lower reactions to food. However the main issue is how food is handled and preserved rather than certain foods always having high histamine.
- 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 they or their toxins might irritate the gut wall and cause release of histamine from mast cells.
- Some people have genetic variants that keep them from making enough diamine oxidase (DAO) while some people have acquired histamine intolerance that may be transient. Acquired histamine intolerance may be due to using DAO blocking drugs, histamine-N-methyltransferase (HTNM) blocking drugs, gut dysbiosis or pathogens or may be due to intestinal inflammation and damage from toxins or disease.
- The most common reason for histamine intolerance is a lack of adequate DAO and it can be replaced.
- Histamine in the gut is taken up into the bloodstream and increased plasma concentrations of histamine can cause symptoms elsewhere. Additionally, metabolites of histamine may also inhibit HNMT which is the intracellular enzyme that breaks down histamine.
What This Article Covers
- How to lessen histamine from forming in food
- Foods likely to be high in histamine
- The use of specific probiotics to compete with commensul bacteria overgrowth that make histamine
- Treating health conditions that induce histamine release by mast cells
- How to remove histamine from the body by the use of supplemental enzymes
- How to decrease histamine release by stabilizing mast cells
- Know the drugs or supplements that cause increases in histamine by blocking or stimulating histamine production
Diet And Histamine
I have seen so many foods listed on low-histamine diets that if someone followed all of these diets, there would be little left to eat. After reading a lot of research papers, I figured out why this is and found a core principal is often being ignored. Many foods have histadine in them. Histadine is an amino acid found in all protein containing foods. Bacteria change histadine into histamine. This means any food that is a protein food that contains histadine can have high histamine levels if bacteria in that food grows. This is why all fish, seafood, slaughtered animals for food, should immediately be refrigerated, frozen or otherwise appropriately processed. If not, bacteria grow and with their growth you get histamine on the rise. Even some fruits and vegetables can have higher histamine than normal in them and these tend to be those fruits or vegetables that are over ripe or that are spoiled. Researchers think histamine is natural in small amounts in many foods, so outright spoilage is not necessary for histamine to exist, but for high histamine to show up in a food it seems to be key for the food to have spoilage or be a fermented product.
If a food is fermented, many of the bacteria used to ferment foods such as bacteria used for lactic acid fermentation in meat, and vegetables or malolactic fermentation in wine will also cause histamine levels to rise.
Therefore, it is more important to make sure you eat only fresh foods and avoid foods that are handled improperly and to be very cautious of foods that are fermented in any way. More research needs to be done on the aspect of fermentation and which bacteria are more likely to increase histamine. We do know that there are some bacteria who use the histadine decarboxylase enzyme (HDC) the same way our cells do to make histamine from the amino acid histadine. These are the bacteria that alter it in food and our gut when they are living in our intestines. We also know some bacteria are known not to do this. Mores studies in the future around bacterial creation of histamine will further our understanding of this matter.
Following are foods that are thought to be high histamine foods most of the time. Other foods you find on high histamine food lists may be high histamine if spoiled, excessively ripe or otherwise contaminated. These or foods similar to these are the ones to really watch out for and avoid, at least initially until one figures out the cause of the high histamine.
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, or freshly frozen or properly canned foods. All food must be fresh before freezing or canning. No old or spoiled food can be used for freezing or canning.
Foods May Cause The Bodies Mast Cells to Release Histamine
We just learned that foods can contain histamine and sometimes in large amounts. Additionally, there are foods thought to stimulate the mast cells in the intestinal wall to release histamine, however research is needed. Some of the foods below are also known to contain histamine normally and sometimes be high in histamine besides possibly causing histamine release by the body. You will note that some of these foods are known So, this makes this a complicated manner to know what is taking place and the research has not caught up with the ideas of clinicians and those who have histamine intolerance. Practitioners can have their patient remove these foods from their diet initially and then reintroduce them to see if they react to them. Some will and some won't. It can also make a difference as to how much of the food is consumed too. Additionally, some of these foods can have higher histamine levels if they are spoiled, not handled properly or otherwise have bacterial growth from fermentation. Therefore, they could be causing histamine reactions simply due to histamine in the food rather than causing mast cell release. Again, this needs further studies to know what is taking place. Additionally, some of these foods can cause IgG reactions, or are high in oxalates and other reasons of sensitivity. I always keep in mind that a person can react to foods for more than one reason.
- Egg white
- Chemicals in the diet
- monosodium glutamate
- food dyes
- food flavorings
- food preservatives
How To Lower All Amines, Including Histamine In Food
We can control the concentration of biogenic amines in our food by targeting the decarboxylase activity in foods. Bacteria make decarboxylase, so aiming to keep them under control is key here.
- Eat fresh food
- When purchasing meat, fish and chicken take a cooler and ice with you to help keep it cool on the way home.
- Refrigerate, freeze or otherwise preserve food immediately if not eating it right away.
- Refrigerate or freeze left overs immediately
The enzyme histadine decarboxylase that the bacteria use to make histamine from histadine in food does not disappear when the bacteria or yeast die. So if there is still histadine in the food (present in protein rich foods), the enzyme can continue to work. It has been shown that freezing the food for 1-2 weeks will inactivate it and cooking the food will destroy the enzyme.
- Watch out for fermented foods
If you are a person interested in fermentation of foods, and you have a histamine intolerance, I suggest you look for starter cultures without decarboxylase activity if that is possible for the fermentation you are undertaking.
Gut flora, Pathogens And Probiotics
In article number one called Histamine Intolerance Causes, Symptoms and Diagnosis, we examine the affect of the pathogens and intestinal flora in our digestive tract and how probiotics could help or hinder the situation. Here we will look more directly at how to deal with these situations.
Pathogens such as parasites, viruses, and bacteria can all cause the mast cells in the intestinal lining to release inflammatory mediators including histamine. This is one source of continual increase in gut histamine and this needs to be dealt with either by using antiparasitics, antibacterials, non histamine producing gut bacteria and/or herbs and supplements to support the immune system. Even commensul bacteria (these bacteria are considered normal and "Kind of friendly" when not in excess and abnormal if they are in excess) can sometimes have overgrowth that needs to be dealt with. In some cases, especially if it is commensul bacteria ( that has grown out of control), simply using healthy, non-histamine producing gut flora is a method practitioners use to compete with the unhealthy growth of the commensuls that are taking over. If however those gut flora are ones that make histadine decarboxylase enzyme (HDC) this will make the individual being treated feel much worse. They will start to shun the use of probiotics. However, if a gut flora replacement is used that is known to not make HDC, this can help to compete for intestinal space and decrease the excessive growth of those out of control commensuls. These gut flora may also be a helpful part of a plan to address the pathogens too. One product I find useful here is made by the company Seeking Health and is called Probiota HistaminX. We won't go into specifics on how to deal with pathogens as different types of pathogens are best dealt with in their own specific ways and the individual person being treated needs to be taken into account as to what their specific needs are also.
One thing to be aware of when suggesting Probiota HistaminX to a patient is that it may decrease bowel motility to some degree. Many folks with histamine intolerance have diarrhea off and on and it may not matter, but some of them have other issues that may be causing them constipation. This could include small intestinal bacterial (or fungal) overgrowth (SIBO or SIFO), dysbiosis, low serotonin or other additional factors causing decreased bowel movements. If there is constipation, they may need to use motility agents or other methods to treat constipation as deemed appropriate for the individual when they first start Probiota HistaminX. This will change depending on the individual. Usually, the decreased frequency or slowing of bowel movements from Probiota HistaminX is temporary and does not last longer than 3-7 days.
Water soluble fiber and gut flora: I would add that some agents used to give bulk to the stool such as water soluble fiber can grow bacteria that may make histamine, so be careful about giving prebiotics such as the various water soluble fibers.
If you don't know what a prebiotic is, it is food that is used for "good gut flora". Many prebiotics are water soluble fibers that also bulk up the stool and are used for constipation. Since water soluble fibers are known as being food for the normal gut bacteria, and some of these normal and "friendly" bacteria will make histamine from histadine, using water soluble fiber might cause those bacteria to grow and cause increased high histamine symptoms.
Fillers and additives: We also need to look at the types of fillers and additives used in encapsulated probiotics as they may trigger mast cells depending on what is used.
The Number One Reason For High Histamine In The Gut
We know that the number one reason for high histamine is due to lack of extracellular or intracellular enzymes to make diamine oxidase (DAO) or histamine-N-methyltransferase (HTNM). The main culprit that appears to be an issue and is the one we can most easily remedy is DAO.
Diamine Oxidase, The Enzyme That Degrades Histamine In The Gut
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 intestinal DAO, and gets into the intestinal wall cells, HNMT inside the cells is there to degrade histamine. In reality there is a little DAO there too as it is made in the cell and secreted into the intestines, but most DAO is in the intestinal lumen and it is largely HNMT that is on duty inside the cell. The HNMT helps prevent 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 and in the gut lumen, 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. A person can be low in DAO due to genetics, or acquired low DAO due to blockage of it being made (drugs or disease) or due to excessive use.
Genetics And Low DAO
Some people have genetic variants that make it harder for them to make adequate enzymes to remove histamine from the body. This is discussed in the Histamine Intolerance Causes, Symptoms and Diagnosis. I have clients with high histamine reactions ask me if this is a permanent condition for them since they have genes that predispose them to this issue. Although, we can't say for sure, it helps to ask when the person first remembers the histamine reactions starting. Are the symptoms life-long or did they start at some defined moment perhaps after a traumatic stress or illness? Those that have had life-long issues, will often continue having issues but can decrease the symptoms tremendously by attending to diet and enzyme support as well as keeping their gut bacteria balanced for the rest of their life. The people who did not have this issue their whole life, may be able to resolve the excess histamine issue as long as another life stressor does not present itself and anything adding to the high histamine is remedied.
Acquired Low DAO
Some people do not have genetic variants known for causing low DAO but they are taking drugs that block creation of DAO or they have inflammation and/or damage to the intestinal lining that can both block DAO and increase histamine release. Additionally, if they are eating high histamine foods or have excessive amount of bacteria making histamine in their gut, this will put a strain on what DAO is available. Intestinal pathogens are another cause of high histamine. Additionally, toxins such as mycotoxins, and other environmental toxins can causes histamine release in the body and add to the histmaine load. Luckily, these acquired factors once recognized can be alleviated, and/or DAO can be supported with dietary nutrients or DAO supplements can be taken with meals. This is usually not a life long issue unless the causative factor can not be found or addressed.
Diamine Oxidase Cofactors Support Creation of DAO
A lack of Vitamin C, Vitamin B-6, Vitamin B1, Niacin, calcium, zinc or copper could cause a decrease in DAO as they are cofactors or otherwise needed for DAO to do its job. Indeed the use of vitamin C and vitamin b-6 have been shown to increase DAO activity.
In one study on atopic eczema and high histamine it was found that even in patients who had low DAO activity that had normal pyridoxal phosphate levels (B6 levels) it was found that supplementing with B6 reversed the low DAO activity. One of the methods clinicians use for patients who have various genetic variants that limit their ability to make an enzyme is to add necessary co-factors to their diet as supplements to see if the increased levels can support an increase in enzymes. The idea being that this individual needs more of some co-factors to get results. The thought is to push creation of as much of the enzyme as is possible. Perhaps that is what is taking place here. I would add though that it is important to not give too much of any one supplement or herb. This can also make a person feel worse. So, when you reach that sweet spot and have enough, be careful not to go over the other side as that will also cause symptoms which is your hint to back off. The hint is when a supplement you take causes an improvement and then you get worse, this is a hint that you may have taken too much. You may need less each day or you may actually need to take it less often.
One study in healthy women showed a variety of nutrients supported DAO enzyme levels. These included:
- long-chain fatty acids, saturated fatty acids, and monounsaturated fatty acids
- saturation fats
- Vitamin B12
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 supplementation. Any respectable 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. If they are not interested in taking a product made from pig kidneys they can still focus 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 primary options in this sitaution.
When DAO Does Not Work
Sometimes a person supplements with DAO and you expect it to work but it does not. They may actually say they feel worse. This is due to another gene not working up to par that needs to process the metabolite that comes from breaking down DAO. When this happens imidazole acetylaldehyde starts to build up. Acetylaldehydes are nasty. Acetylaldehyde is made when alcohol is broken down and anyone who has had a hangover knows what that feels like. So, this gives you an idea of how this person feels. Here is how this all takes place. DAO is broken down into imidazole acetylaldehyde. This metabolite is further broken down into imidazole acetic acid. If the gene that makes the enzyme called aldehydyde dehydrogenase that breaks down imidazole acetylaldehyde into imidazole acetic acid is not working up to par, the increase in imidazole acetylaldehyde will feedback to the gene making DAO and inhibit it. If a person has variant genes for both DAO production and imidazole acetic acid production, taking DAO won't be enough. In this case when the aldehyde dehydrogenase enzyme is also low there are a few things that can be done to try to support increased activity. Zinc and niacin may be helpful if the person is low in either or both of them as they are used as cofactors. If there is adequate zinc and niacin or supplementing with them and the individual is still not getting the results expected, you need to look at other epigenetic factors that will slow down genetic production of aldehydyde dehydrogenase. Things to consider would be reactive oxygen and nitrogen species as well as non steroidal anti-inflammatories, aspirin and oxidzed fatty acids in the diet.
Additional Enzymes Used In Degradation Of Histamine
Monoamine oxidase (MAO)
Monoamine oxidase enzyme is also used to lower histamine levels in the brain. Here in the brain after histamine has been altered to N-methyl-histamine by HNMT, MAO-B next alters N-methyl-histamine to 1-methylimidazole-4-acetaldehyde. S-adenosyl-methionine (SAM or SAMe) is needed in this reaction to supply the methyl group.
Riboflavin and iron are necessary for the activity of this enzyme - look at iron and iron storage in the patient. Consider iron supplementation if there is a "low normal" iron level and the storage iron (serum ferritin) is low. A study showed a low MAO activity in histamine intolerant test subjects was restored with iron and B2 (riboflavin) supplementation. Vitamin C is also helpful in supporting MAO.
MAO-A is primarily found in the stomach, and intestine while MAO-B is found in the brain.
Histamine N-methyltransferase (HNMT)
Histamine N-methyltransferase (HNMT) acts intracellularly and is key in high histamine states in the respiratory tract. It does not play a direct role in metabolism of food based histamine or histamine released into the gut by bacteria. It plays an indirect role in that the HNMT enzymes are made and used intracellularly including the gastrointestinal cell lining. Both DAO and HNMT are made in these cells lining the digestive tract, but DAO is mostly released into the gut while HNMT stays in the cells. Therefore, if the histamine gets into the cells from the gut, the HNMT has a chance to help degrade it before it ends up in the blood stream. Additionally, since HNMT is found in many cells all over the body it does lower the overall histamine load of the body by acting intracellularly and lowering whole body histamine burden. It should not be discounted completely as has been done in the past. If it too has genetic variants causing decrease creation of HNMT, this will definitely add to the histamine body load. Part of the reason for discounting it may be that we have no way to replace it and there is less known about how to support it.
Methylation needs to be working properly for HNMT enzyme activity, so methylation support is necessary if the person is known to have a methylation issue from genetic variants or from acquired reasons.
Support with nutrients known to help includes: Vitamin A, Vitamin D, molybdenum, copper, selenium zinc
Drugs known to block DAO and HNMT Production
There are a number of drugs that are known to block either DAO or HNMT and they may be adding to the excess histamine level in their body. It is important to take a look at the drugs your patient is using (supplements too) and see if they are on this list. You will find the lists in the article called Histamine Intolerance Causes, Symptoms and Diagnosis.
Stabilizing Mast Cells and Antihistamine Activity
We have examined food borne histamine and histamine made by bacteria in the gut. We know that pathogens and some overgrowth of commensuls can cause intestinal wall inflammation and damage as well as induce release of mast cell inflammatory mediators including histamine. One way to counter this is to help stabilize the mast cells so they don't release as much histamine when confronted with pathogen toxins, environmental toxins or allergens. There are numerous types of supplements, herbs and dietary additions that are used to do this. Here are some of the more well known ones. However, keep in mind that many colorful fruits and vegetables are found to be useful in this aspect.
- Fish oil to stabilize cell membranes and decrease inflammation/histamine leakage from mast cells
- Vitamin C to stabilize mast cells - small doses often through-out day or 30 minutes before meals.
- Quercetin - high doses are often helpful - 500 mg 4 times per day or more if the physician feels it is necessary. Starting slowly moving up to this dose over a couple weeks. Some people may react to it and need super low doses initially or a change to a different supplement.
- (Neuroprotek LP - 40 mg) Take 30 minutes before meals and one before bed.
- A study found mung bean sprouts (48 hours of sprout growth) provided significant protection against mast cell degranulation and histamine release due to their high flavonoid content. - 30 minutes before meals.
- Methylation support as practitioner feels needed if methylation is not up to par as HNMT won’t work well with decreased methylation (most of your methylation activity goes to produce phosphatidylcholine and creatine, so some practitioners supplment these if methylation is an issue for the individual)
Methylation support is important If there is impaired methylation due to MTHFR single nucleotide polymorphism consider support of methylation with Vitamin B12 as meythylcobalamin, methylfolate, B6 (as pyridoxal 5 phosphate), trimethylglycine, choline, magnesium, zinc and riboflavin.
- Perimine (extract of Perilla seed) - One capsule 30 minutes before meals.
- AllQlear - Made from quail eggs. Contains a tryptase blocker - tyrptase is another mediator released from Mast cells. 1-2 tablets 30 minutes before meals.
- Licorice - not to be used if there is high blood pressure or edema
- Turmeric - Curcuma longa (curcumin studied)
- Glutathione - antioxidant that helps to neutralize inflammatory mediators. If there is not enough, this will add to the inflammation as oxidative stress will result in mast cells releasing more chemicals and there will be more histamine. There will be further need for neutralizing the inflammatory mediators made by the mast cells and more need for glutathione. You can see an inflammatory circle is created here. Glutathione and other sulfur containing supplements and food can feed bacteria in the colon that makes hydrogen sulfide and can lead to dysbiosis in some cases. If this happens you probably have an overgrowth of these bacteria and will want to decrease them. You will also need to back off on the sulfur containing supplements a bit perhaps until this is resolved.
- Some probiotics are helpful in normalizing gut health when there is dysbiosis and are not found to add to the high histamine load. Bifidobacterium spp. have been shown to often be helpful, while many Lactobacilli produce histamine but Lactobaccilus plantarum and Lactobaciilus rhanosus may downgrade bogenic amines including histamine making them beneficial strains possibly for folks with high histamine. However, I have seen conflicting research and at this point feel there is a lot of confusion around this. Some of this confusion may be due to the differences found in various strains. For instance it appears at this writing that the strain Lactobacillus plantarum D-1033 and Lactobacillus rhamnosus GG strain appear to downregulate IgE and histamine receptors and up-regulated anti-inflammatory agents in the gut helping to reduce overall histamine, decrease intestinal permeability and keep pathogenic bacteria from adhering to the gut wall. I have been using a product named Probiota Histaminx that has bacteria in it that appear not to make histamine and are beneficial in lowering histamine levels and crowing out the bad bacterial players.
Polyphenols And Mast Cell Stabilization
Foods high in a class of polyphenols called flavonoids are able to assist in decreasing mast cell activation and reduce histamine in the body. These flavonoids include quercetin and catechin which are found in herbs such as Green tea, Chamomile, Hawthorne and Gingko. Quercetin is found in many foods/herbs and some good choices for quercetin content are garlic, onions, capers, fruits with dark red or blue colors such as blueberries and cranberries. Elderberries are high in quercetin as well as Lovage and kale. Quercetin’s anti-inflammatory activity appears to be due to its antioxidant effects and inhibition of cyclooxygenase and lipoxygenase, which in turn regulate the inflammatory mediators leukotrienes and prostaglandins. Quercetin has been shown to stabilize mast cells, which inhibits release of histamine by the mast cells.
Foods and Spices To Consider Adding Into Diet To Help
- Pea sprouts
- Black cumin
Research Studies Identified Herbal Constituents That Stabilize Mast Cells
- Epigallocatechin gallate found in Green tea – Camellia sinensis can inhibit the release of histamine from mast cells.
- Theanine is another constituents found in Green tea - Camellia sinensis. This amino acid has been shown to prevent histamine release from cells when in low concentrations.
- Ellagic acid found in fruits such as raspberries, strawberries, walnuts and pomegranate inhibit histamine release as well as proinflammatory cytokines such as TNF-alpha and Il-6.
- Khellin from the herb Khella – Ammi visnaga has been shown to stabilize mast cells. This is also an herb that is used to prevent Asthma attacks. I have found it especially useful in the past for exercise induced asthma. Khella is not an herb that is used for immediate relief, and high doses may cause side effects such as liver damage.)
- Silibinin from the herb Milk thistle- Silybum marianum prevents histamine release as well as preventing release of other inflammatory cytokines from mast cells.
- Reservatrol found in the herb Japanese knoteweed - Polygonum cuspidatum, as well as the foods grapes, peanuts, and blueberries, was found to suppress inflammatory cytokines linked to mast cell disorders, specifically tumor necrosis factor and interleukins.
- Curcumin from the herb Turmeric – Curcuma longa prevents release of histamine by stabilizing mast cells and inhibits cytokines IL-4 and TNF-alpha.
- Parthenolide from the herb Feverfew – Tanacetum parthenium stabalizeds mast cells.
- Indoline from the herb Woad - Isatis tinctoria stabilized mast cells.
- Estragole from the herb Basil - Ocimum basilicum reduces inflammation due to edema and arachidonic acid.
What We Learned
- The most common reason for histamine intolerance is a lack of adequate DAO and it can be replaced with DAO enzyme made from pig kidneys.
- To lower our histamine burden we can eat fresh foods or properly prepared and preserved foods. Additionally, high histamine foods can be avoided initially.
- Adequate nutrients are necessary to make DAO and can be used to stimulate production in both genetic and acquired deficiency.
- Supplements and herbs can be used to stabilize mast cells and decrease histamine release.
- Additionally, we can use non-histamine producing bacteria as flora replacement to compete for space in the colon with the bacteria that are making histamine. Some of these flora have been shown to act in a variety of ways to lower histamine and make the gut healthier.
- Some drugs will block DAO production or stimulate mast cells to make histamine. These should be avoided if possible.
- Any pathogens or dysbiosis should be attended to as it can be a primary cause of acquired histamine intolerance.
- Toxins from the environment need to be dealt with as they too can cause histamine release from the mast cells.
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