Could a low-histamine diet be the solution to your health problems? Do you suffer from any of the following? Headaches/migraines

Asthma

Itching

Puffy eyes

Facial flushing

Hives

Pre-menstrual cramps

Cough

Palpitations or racing heart

Swelling of ankles/feet

Low blood pressure

High blood pressure

Insomnia

Abdominal pain, gas, bloating, diarrhea If so, you’re not alone. MANY people have at least one of the problems listed above but might never suspect that the culprit could be right in front of their noses—on their dinner plates! These symptoms can all be caused by a tiny but powerful natural substance called histamine. 1 Anybody can have histamine intolerance, but you are at higher risk if you eat a GAPS diet or a low-carb diet, enjoy gourmet foods, or have been swept up in the current fermented foods fad. That's because histamine is found lurking primarily in aged, fermented, cured, cultured, and smoked foods. Foods like aged beef, ripe cheeses, salami, sauerkraut, red wine, and natto can all be quite high in histamine. Histamine intolerance symptoms tend to appear very soon after eating a high-histamine food, typically within less than two hours. Symptoms typically disappear in a matter of hours and rarely last longer than 24 hours. 2 These symptoms aren’t proof positive of a histamine problem; it is also possible that you have other food sensitivities or health problems, which we’ll discuss later in this article. This post is dedicated to the practical aspects of histamine intolerance, such as diagnosis, prevention, treatment, food choices, food handling/storage, and medications to avoid. To learn about the biology and chemistry behind this diagnosis—what histamine is, how it forms, how it behaves in our bodies and why some people are more sensitive to it than others, please see my companion post: "Histamine Intolerance: Understanding the Science."

Histamine intolerance in a nutshell Histamine is an important molecule used to regulate body functions, so it’s found naturally in our bodies in tiny amounts for good reason. The problem is that it is also found in aged foods. If you have healthy gut defenses, you can handle reasonable quantities of histamine in foods. However, more and more of us have compromised gastrointestinal systems and so have difficulty with even small quantities of natural food toxins like histamine. If too much histamine makes its way from foods into your bloodstream, it can cause a wide variety of unpleasant symptoms. If you eat too much histamine or are sensitive to histamine, you can experience all kinds of annoying symptoms that most people wouldn’t think of as related to diet, including asthma, panic attacks, pre-menstrual cramps, and sleep disturbances. My story Histamine intolerance is much more common than most people realize. Most people who have it don’t realize it—I was one of them! Years ago when I first turned my diet upside-down and started eating a low-carbohydrate, high-fat, mostly-meat diet, my health improved tremendously in every way. Yet there were still some frustrating symptoms that would crop up every once in a while: IBS, fatigue, insomnia, ankle swelling, itchy skin, dry cough, and environmental allergies. I couldn’t tell which foods were the culprits. Sometimes fish or beef or pork would bother me and other times it wouldn’t. Some processed meats agreed with me while others didn’t. In 2013 I started a blog series about a new ketogenic diet I was experimenting with, describing how I felt along the way. It was then that Dr. Judy Tsafrir wrote in and suggested I might have histamine intolerance. And by gum, she was right! This eureka moment was what inspired me to write these articles for you. Who is at risk for histamine intolerance? Histamine intolerance affects at LEAST 1% of us, but the majority of people with histamine intolerance go undiagnosed, so the actual prevalence is surely much higher. 1 Eighty percent of histamine intolerance sufferers are middle-aged, and the vast majority are female. 2 Other risk factors for histamine intolerance include: 3 Gastrointestinal damage (crohn’s, celiac, intestinal surgery, chemotherapy)

Deficiencies in vitamin B6, vitamin C, zinc, or copper

Genetic abnormalities in DAO (diamine oxidase), the primary enzyme responsible for protecting us from histamine in foods

Taking a medication that interferes with histamine metabolism How much histamine can you tolerate? Levels exceeding 2 mg/L in beverages and 50 mg/kg in foods are considered risky 4 even for healthy individuals without histamine intolerance, because the human body has a limited capacity to handle histamine in foods. People with histamine intolerance tend to react to even lower levels because they are especially sensitive. Foods high in histamine Nearly all foods contain at least a small amount of histamine, so it’s impossible to completely avoid it. However, some foods are MUCH higher in histamine than others. Unfortunately, histamine levels in foods vary WIDELY. For example, like other animal foods, fresh tuna is very low in histamine, whereas levels in canned tuna can range anywhere from zero to as high as 40.5 mg/kg. So as you’ll notice, most histamine levels in the tables below are listed as ranges rather than absolute values. Unless you have your own personal chemistry lab, it is simply impossible to know how much histamine is in any given food. However, there are general guidelines that can help you guess whether a food is likely to be lower or higher in histamine. Any high-protein food (meat, poultry, seafood) that isn’t absolutely fresh will contain rising levels of histamine. The less fresh it is, the more histamine it will contain. Examples include aged beef, leftover chicken salad stored for too long in the refrigerator, and fish that takes a long time to travel from the boat to the grocery store

will contain rising levels of histamine. The less fresh it is, the more histamine it will contain. Examples include aged beef, leftover chicken salad stored for too long in the refrigerator, and fish that takes a long time to travel from the boat to the grocery store Most aged, cultured, fermented, smoked, and cured foods and even some cultured beverages

and even some A handful of fresh plant foods that are naturally high in histamine

Beverages Champagne 670 mg/L Red wine up to 24 mg/L Coffee <2mg/L Plant foods Most (fresh) vegetables are very low in histamine, with levels ranging from 0 to 16 mg/kg. The notable exceptions are tomatoes, eggplant, and spinach: Ketchup 22 mg/kg Eggplant 26 mg/kg Spinach 30 to 60 mg/kg Avocado 23mg/kg Sauerkraut (fermented cabbage) up to 229 mg/kg Miso (fermented soybeans) 3 to 6 mg/kg Natto (fermented soybeans) can reach over 50mg/kg Dairy products Uncultured dairy products such as milk and cream tend to be very low in histamine, with levels of less than 1 mg/kg. The same is true for fresh, unripened cheeses with short shelf-lives, such as fresh mozzarella and ricotta. Sour cream up to 7 mg/kg Yogurt up to 13 mg/kg Ripened cheeses 2.21 – 2500 mg/kg (whoa…) Meat Most fresh meats are very low in histamine. Dry sausages such as salami, pepperoni, and chorizo, are the meat products highest in histamine content. Dry aged sausages up to 357 mg/kg

Fish Certain kinds of fish are more likely to contain high amounts of histamine unless they are very fresh, because they are naturally higher in the amino acid histidine, which bacteria can turn into histamine. Amberjack Herring Tuna Anchovies Mackerel Pilchards Bluefish Mahi Mahi Sardines Cape Yellowtail Marlin Trigger foods Some foods are suspected of triggering histamine release within some people’s bodies, even though they may not contain much histamine of their own. Citrus fruits Crustaceans Spices Peanuts Fish Chocolate Additives Strawberries Licorice Pineapple Tomatoes Egg white Spinach Papaya Pork Nuts

How is histamine intolerance diagnosed? If you have at least two typical symptoms (listed at the top of this article) and they go away either with a low-histamine diet or with the use of antihistamine medications, then you probably have histamine intolerance. As with any food sensitivity issue, keeping a careful food-symptom diary is very important in noticing patterns. There are many possible food culprits in the world that have nothing to do with histamine intolerance, so you may discover some surprising food reactions if you pay close attention.

Keeping an accurate food diary— food and drink consumed, mood, symptoms, sleep, exercise, and medications—can reveal patterns and identify problem foods in your diet. This is a powerful tool in reclaiming your good health. There are numerous good mobile apps available.

People who suspect they may have histamine intolerance should first be tested for true food allergies to rule those out before undergoing more specialized testing. Food allergies can cause a lot of the same symptoms that histamine intolerance can. Other possible conditions that can mimic histamine intolerance Include: Non-histamine food intolerances

Mast Cell Activation Syndrome, a condition in which histamine-producing mast cells in the immune system are too reactive 1

Mastocytosis, a rare genetic excess of mast cells There is a variety of methods you and your doctor can use to figure out whether you might have histamine intolerance, but most available tests are imperfect. This means that even if you “test negative” for histamine intolerance, you could still have it. That’s why I believe the best approach is to eat a low-histamine diet for a few weeks to see if your symptoms go away. If they do, you’ve solved your own problem and you may decide you don’t need further proof or validation! Serum DAO level Activity levels of DAO—the enzyme that destroys histamine–can be measured using a blood test: “Histamine intolerance is presumably highly likely in patients with DAO activity <3 U/mL, likely (but less likely) in patients with DAO activity <10 U/mL, and improbable in patients with DAO activity >10 U/mL.” 2 However, this method is considered fairly unreliable, because blood levels of DAO are so unstable. Even if your DAO blood test comes back normal, there is still a 50% chance that you have histamine intolerance (false-negative). If your DAO blood test comes back abnormal, there is a 17% chance that you DON’T have histamine intolerance (false-positive). Oral histamine challenge Many physicians consider this test to be the gold standard for diagnosis of histamine intolerance. It involves following a strict low-histamine diet for four weeks, and then undergoing a “histamine challenge” in which you are asked to swallow capsules filled with pure histamine (typically a 75 mg dose) while a clinician monitors your medical reaction for signs and symptoms of histamine intolerance. Unfortunately, this test can also be misleading, because there are many people with histamine intolerance who do not react to pure histamine and pass this test with flying colors. They look and feel perfectly fine. Why would that be? If you are sensitive to histamine, and someone gives you pure histamine, shouldn’t you have a bad reaction? Here’s the thing: pure histamine does not exist in nature. In real life, histamine exists in foods, some of which can affect the way we respond to histamine. To make matters more complicated, histamine is always accompanied by related substances (other biogenic amines) in aged foods that magnify our reaction to histamine. There are also many other factors that can influence how you respond to histamine from one day to the next [see section below entitled confounding factors]. In addition, oral challenge tests are expensive and time-consuming, so they may not be offered by your doctor’s office and/or may not be covered by your medical insurance plan. Intestinal biopsy DAO levels in the cells lining the gut can be measured directly if you undergo an endoscopy and have small samples of your intestinal cells biopsied for laboratory testing. This test is the real gold standard, because most cases of histamine intolerance are thought to be due to reduced levels of DAO in the cells lining the gastrointestinal tract. 3 Naturally, the biopsy test is rarely performed, because: it is an invasive surgical procedure

it is expensive

it is highly unlikely that your insurance would cover it Histamine skin-prick test This is probably the best test available because it’s inexpensive, simpler, and more accurate than other readily available office tests. In this test, your skin is punctured with histamine. If you develop a “wheal” (bump) on your skin that is still visible 50 minutes later, it is likely that you have histamine intolerance. Whether you test positive or negative for histamine intolerance by skin testing, there is about a 20% chance that the test result is wrong. 4 Beyond histamine Unfortunately, symptoms of histamine intolerance are not simply about how much histamine is in the foods we eat. There are many other things that influence how we respond to histamine in foods, which can make things quite confusing for patients and doctors alike. Below are common reasons why we might have different reactions to the same food on different days. Some medications interfere with DAO activity, including NSAIDS such as Ibuprofen 5

Estrogen stimulates histamine production 6

Stress and physical injury trigger immune cells to release histamine and other pro-inflammatory substances 7

Alcohol interferes with DAO activity, which can increase our exposure to histamine 8

Histamine is always accompanied by a posse of other “biogenic amines” which can worsen our response to histamine depending on which ones are present and how high the levels of each of them are. 9 Is histamine intolerance real? Although the concept of histamine intolerance is gaining ground, there is considerable controversy around this diagnosis, and many scientists and physicians still think of histamine intolerance as only weakly grounded in scientific evidence or perhaps even psychosomatic in nature. It is easy for doctors to be skeptical: Tests for histamine intolerance are often inaccurate

A person’s reaction to high-histamine foods can vary from day to day

Some doctors may not understand the complexity of the science behind histamine intolerance My philosophy is this: if you notice that foods high in histamine bother you, you don’t need a scientist or a doctor to prove you right. Food handling and storage tips to minimize histamine exposure Of course, simple, natural, preventive measures are usually the wisest course of action. Understanding how histamine forms in foods can help you to minimize your exposure not just to histamine, but to all potentially irritating and/or toxic biogenic amines.

Once histamine is in a food, there’s no getting rid of it; it is not destroyed by cooking, freezing, hot smoking, or canning.

Histamine is indestructible. Once histamine develops in a food, there’s no getting rid of it. And if bacteria or yeast are still present in the food, histamine levels will only continue to rise. So here’s what you need to know: 1 Immediate storage of meats and fish on ice dramatically reduces the rate of histamine formation (but does not stop it completely). If you can bring a cooler with some ice in it to your grocery store, you can keep histamine levels from rising in your warm car on the way home.

HDC (histidine decarboxylase) is the enzyme that bacteria and yeast use to create histamine from proteins in our foods. HDC can remain in foods even after the bacteria (or yeast) that produced that enzyme have died off. Therefore, HDC can remain active, turning proteins into histamine, long after the micro-organisms are dead and gone, leading to continued accumulation of histamine. Fortunately, HDC can be inactivated by freezing for 1-2 weeks, and is destroyed by cooking.

Histamine itself is NOT destroyed by cooking, freezing, hot smoking, or canning. Therefore, once it has been produced, you are stuck with it.

Histamine itself has no flavor and is odorless, so you can’t use the “smell test” to detect its presence. Treatment of histamine intolerance If you suspect you have histamine intolerance, here are some options which may help you to feel better: Eat a low-histamine diet. Avoid cultured, processed, cured, fermented and aged foods. Choose fresh foods whenever possible. Look for the “packed on” date of the meat or fish being sold. “FAS” (frozen-at-sea) fish may be your best bet. Grass-fed and pastured meats are not necessarily better choices—it depends on how far they had to travel to get to your store. Also, it is important to know that nearly all beef sold in the U.S. “hangs” for at least two weeks before it is packaged, even if it comes from a local family farm that pastures their animals. Therefore virtually all beef is aged to some extent. Yasmina Ykelenstam’s website contains a wealth of information about low-histamine diets: http://thelowhistaminechef.com/ Occasional use of antihistamines such as Diphenhydramine (Benadryl) and Cetirizine (Zyrtec), or “mast cell stabilizers” such as Cromolyn Sodium (Gastrocrom) may be helpful if they don’t bother you. Vitamin C, vitamin B6, zinc, and copper are all required for DAO to work properly. Addressing potential deficiencies in these may be helpful in resolving histamine intolerance.

DAO supplements are available and have been proven effective. 1 The one I use is from Seeking Health. This supplement contains DAO enzymes isolated from pig kidney. It also contains a small amount of vitamin C, which helps DAO to work better. While I generally try to avoid high-histamine foods, life happens. When I’m traveling, eating at someone else’s home, or not sure about the histamine content of a food, I use this supplement to help minimize symptoms of histamine intolerance from foods I suspect may bother me. It needs to be taken right before you eat—no longer than 15 minutes– so that it will be in the right place at the right time—in your small intestine when the suspicious food arrives.

Some people, especially those with prominent gastrointestinal symptoms of histamine intolerance may benefit from pancreatic enzymes. 1 Avoid alcohol—alcohol reduces DAO activity. Be aware of medications that interfere with DAO activity. If you take any of the following medicines, discuss with your clinician how they may be affecting your histamine intolerance symptoms, to see if alternatives are available. 2 Bottom line? Eat fresh (and I don’t mean at Subway . . . )

Hungry for more histamine knowledge? Please see my companion post: "Histamine Intolerance: Understanding the Science" which explores the fascinating world of biogenic amines, how histamine forms inside and outside of our bodies, how and why histamine affects our physical and mental health, why some people, especially women, are more sensitive to histamine than others, and why reactions to high-histamine foods can be so unpredictable and confusing. To learn about the connection between food sensitivities and anxiety or insomnia, including the possibility that histamine is keeping you up at night or causing panic attacks, I recommend reading my Psychology Today article "5 Foods Proven to Cause Anxiety and Insomnia." You can also listen to my podcast interview with Yasmina Ykelenstam, the Low Histamine Chef, about the connection between histamine intolerance and mental health.