HISTAMINE AND TYRAMINE SENSITIVITY
BIOGENIC AMINES INTOLERANCE: HISTAMINE AND TYRAMINE SENSITIVITY
Biogenic amines, including histamine and tyramine, are products of certain amino acids that make up specific proteins. They may be present in both plants and animals consumed as food. In fact, small quantities of biogenic amines are present in almost all foods and usually cause no problems. Large quantities result from microbial activities during rotting of foods and during manufacture of fermented foods such as cheese, wine, vinegar, fermented sausages, soy sauce, and sauerkraut. Large quantities, especially of histamine in foods, cause symptoms of food poisoning in most people; individuals who are considered “intolerant” to biogenic amines experience symptoms when they consume levels that cause no problems in nonsensitive people.
Varying opinions exist on the significance of biogenic amines in non-immunologically-mediated reactions to foods. Because histamine is the most important mediator responsible for the symptoms of “classical allergy” in the Type I (IgE-mediated) hypersensitivity reaction, it is difficult for clinicians to distinguish between reactions due to allergy and those resulting from too much histamine, since the symptoms are the same in both cases. The “classical” symptoms of food allergy, such as urticaria (hives), angioedema (tissue swelling), nasal congestion, asthma (in asthmatics), headaches, oral allergy symptoms, and digestive-tract complaints such as nausea, flatulence, abdominal cramps, and diarrhea, are also typical of histamine intolerance and, to some extent, tyramine intolerance.
HISTAMINE
Histamine is an important physiological fluid in the body. It is always present in plasma, the fluid portion of blood in which blood cells are suspended. The level of histamine in blood goes up and down throughout the day in a specific type of rhythmic variation. Histamine plays important regulatory roles in gastric acid secretion in the stomach, in determining how easily substances pass through blood vessels, in muscle contraction, and in the immune response. It is a key mediator in inflammation, which is the way the immune system protects the body from invasion by infective microorganisms and other events, such as trauma (tissue injury), that are a threat to health.
Histamine is manufactured and stored in a number of cells in the body, particularly mast cells, which occur throughout body tissues, especially mucous tissue. In an allergic reaction (IgE-mediated Type I hypersensitivity), histamine is released from mast cells in vast quantities and is one of the most important inflammatory mediators of the swelling, itching, reddening, and increased movement of blood cells and fluid from inside blood vessels into tissues that are characteristic of symptoms of allergy.
Events other than Type I hypersensitivity can cause the release of histamine from mast cells. Some foods and food additives have shown this ability in the absence of allergy.
Histamine Intolerance
High doses of histamine are toxic for all humans, but individual tolerance determines reactivity to small quantities. Just about everyone who ingests histamine from a contaminated food at a level of more than 2.7 milligrams per kilogram of body weight will show symptoms of “histamine poisoning,” but at lower concentrations only a few sensitive individuals will have a reaction. It is likely that differences in levels of tolerance are of genetic origin, but tolerance can be reduced by disease, especially allergy and autoimmune diseases and medications, such as some antidepressants, some asthma medications, and some antihypertensive drugs.
Cause of Histamine Intolerance
The cause of histamine intolerance is thought to be a defect in the breakdown of histamine. In humans, breakdown of histamine is done by two enzymes, diamine oxidase (DAO) and histamine methyltransferase (HMT), that have different characteristics. DAO occurs predominantly in the lining of the intestine as well as the placenta, kidney, and the thymus gland. HMT has a wider distribution, occurring in the stomach, lung, spleen, kidney, thymus, and particularly the brain. Both enzymes can be slowed or stopped by a variety of compounds, many of which are used as medications. Reduced DAO activity has been the subject of several investigations of conditions such as “idiopathic” (of unknown cause) urticaria and angioedema in which an allergic response has been ruled out. Laboratory findings of increased plasma levels (greater than 2 nanograms per milliliter) of histamine and reduced DAO activity have been suggested as indicators of reduced histamine breakdown and possible enzyme deficiency.
Symptoms of Histamine Intolerance
Symptoms occur when the enzyme system that breaks down histamines cannot keep the histamines at a “normal” level.
Urticaria (hives) and angioedema (tissue swelling) are symptoms that occur in response to excessively high levels of histamine in the body. Rhinitis (nasal congestion) is another symptom of too much histamine. Histamine has also been implicated as an important mediator in some types of headaches that are thought to differ from migraine.
Histamine is the only proven inflammatory mediator to cause itching. Histamine can also cause blood vessels to become more permeable, thus allowing fluid to move from the blood vessels into tissue, causing swelling. It can also cause blood vessels to widen. Sensitive people may experience symptoms such as hypotension (drop in blood pressure) and tachycardia (increased pulse rate) as a result.
Dietary Management of Histamine Intolerance
A histamine-restricted diet has often proved beneficial in reducing total body histamine levels when the cause of the condition is unknown but the symptoms indicate that histamine is the principal mediator. Conditions such as idiopathic urticaria (chronic hives of unknown cause), angioedema (“giant hives”), chronic itching, and some headaches have responded well to a histamine-restricted diet. It is worthwhile to restrict these foods for four weeks in cases where all other treatments have not helped relieve symptoms.
SYMPTOMS INDICATING TOO MUCH HISTAMINE IN THE BODY
| ♦ rhinitis and rhinorrhea (stuffy, runny nose) |
| ♦ conjunctivitis (irritated, watery, reddened eyes) |
| ♦ urticaria (hives) |
| ♦ angioedema (swelling, especially of facial tissues) |
| ♦ itchiness (especially of eyes, nose, ears, skin) |
| ♦ headache |
Food Sources of Histamine
Histamine is present in most fermented foods. Microbial enzymes convert the amino acid histidine (present as a part of all proteins) to histamine. Any foods that have been subjected to microbial fermentation in the manufacture of the food, such as cheeses, fermented soy products, fermented foods (sauerkraut), alcoholic beverages, and vinegars, contain histamine.
Foods that have been exposed to microbial contamination will contain histamine; the level is determined by how fast the microbial metabolism takes place. Histamine levels will rise to a reactive level long before any signs of spoilage occur in the food. This is particularly important in fish. Bacteria in the gut will start to convert histidine to histamine as soon as the fish dies. The longer the fish remains ungutted, the higher the level of histamine in the flesh.
Some foods, such as tomato, eggplant, and spinach, contain high levels of histamine naturally. In addition, a number of food additives such as azo dyes, particularly tartrazine, and preservatives are known to cause histamine to be released. Some of these (such as benzoates) occur naturally in foods, especially fruits, and may have the same effect as the food additive in releasing histamine. The histamine-restricted diet excludes all the foods that are known to contain high levels of histamine. It also excludes chemicals that can release histamine when they enter the body.
Histamine excess is dose-related. Each function and food adds its own level of histamine up to the person’s limit of tolerance. Once the limit is reached, histamine “overflows” and symptoms result (Figure Diagram Representing a Person with Allergies to Pollen and Cat Dander
Who Has Eaten a Meal Containing Histamine-Rich Foods (Cheese, Tomato, Strawberries) with Wine). The severity of the symptoms depends on the amount of excess histamine in the system.
General Instructions for Avoiding Histamine-Rich Foods
Meat, Poultry, Fish, Egg
Avoid the following:
♦ Fish and shellfish whether fresh, frozen, smoked, or canned, if processing is unknown. If the fish is freshly caught, gutted, and cooked within ½ hour, it may be eaten.
♦ Egg. A small quantity of cooked egg in a baked product such as pancakes, muffins, and cakes is allowed.
♦ Processed, smoked, and fermented meats such as luncheon meat, sausage, weiner, bologna, salami, pepperoni, smoked ham, cured bacon.
♦ Left-overs. Freeze any uneaten protein-based food. Bacteria will quickly act on protein at room and refrigerator temperatures, resulting in histamine production.
Milk and Milk Products
Avoid all fermented milk products, including
| ♦ Cheese of any kind such as cheddar, Colby, blue cheese, Brie, Camembert, |
| feta, Romano |
| ♦ Cheese products such as processed cheese, cheese slices, cheese spreads |
| ♦ Cottage cheese |
| ♦ Ricotta cheese |
| ♦ Yogurt |
| ♦ Buttermilk |
| ♦ Kefir |
Fruits
Avoid
| ♦ Orange, grapefruit, lemon, lime |
| ♦ Cherries |
| ♦ Grapes |
| ♦ Strawberries |
| ♦ Apricots |
| ♦ Avocado |
| ♦ Raspberries |
| ♦ Pineapple |
| ♦ Cranberries |
| ♦ Prunes |
| ♦ Loganberries |
| ♦ Dates |
| ♦ Raisins |
| ♦ Currants (fresh or dried) |
Vegetables
Avoid
| ♦ Tomatoes, tomato sauces, ketchup | ||
| ♦ Soy and soy products | ||
| ♦ Spinach | ||
| ♦ Red beans | ||
| ♦ Eggplant | ||
| ♦ Olives in vinegar or brine | ||
| ♦ | Pumpkin | |
| ♦ | Pickles, relishes, and other foods containing vinegar | |
Food Additives
Avoid
| ♦ Tartrazine and other artificial food colors |
| ♦ Preservatives, especially benzoates and sulphites |
Seasonings
Avoid
| ♦ Cinnamon |
| ♦ Cloves |
| ♦ Vinegar |
| ♦ Chilli powder |
| ♦ Anise |
| ♦ Curry powder |
| ♦ Nutmeg |
Miscellaneous
Avoid
| ♦ | Fermented soy products (such as soy sauce, miso) |
| ♦ | Fermented foods (such as sauerkraut) |
| ♦ | Tea (regular or green) |
| ♦ | Chocolate, cocoa, and cola drinks |
| ♦ | Alcoholic beverages of all types |
| ♦ | “De-alcoholized” beverages (e.g., beer, ale, wine) |
Medications and Vitamin Supplements
♦ Tartrazine is in some medications (both prescription and nonprescription) and some vitamin supplements. Essential medications should be tartrazine -free.
♦ Pharmacies keep a list of manufacturers who produce tartrazine-free products.
Contact Allergy
♦ Some toiletries and cosmetics containing histamine-releasing substances may cause contact dermatitis. Avoid any that contain cinnamaldehyde, Balsam of Peru, benzoates of any type, sulfites, and dyes.
Figure Diagram Representing a Person with Allergies to Pollen and Cat Dander
Who Has Eaten a Meal Containing Histamine-Rich Foods (Cheese, Tomato, Strawberries) with Wine
The Histamine-Restricted Diet
Table The histamine-restricted diet lists the foods allowed and the foods not allowed in the histamine-restricted diet. This diet excludes all:
♦ Foods with naturally high levels of histamine
♦ Fermented foods
♦ Artificial food colors, especially tartrazine
♦ Preservatives, particularly benzoates and sulphites
Table The histamine-restricted diet
| Type of Food | Foods Allowed | Foods Restricted | |
| Milk and
Milk Products |
• Plain milk
• Cream • Ice cream without artificial additives • Curdled milk products |
• Any manufactured dairy products
made with restricted ingredients • Cheese of all types • Yogurt • Buttermilk • Any milk products produced by fermentation |
|
| Breads
Cakes and Cookies Breakfast Cereals Crackers Pasta and Noodles |
• Any unbleached flour
or grain • Corn; cornstarch and plain popcorn • Plain rice and wild rice • Parboiled rice • General Foods Minute Rice • Any plain fresh whole-grain bread, buns, biscuits, pizza dough with allowed ingredients. • Homemade or purchased baked cookies, pies, etc., made with allowed ingredients • Breakfast cereals with allowed ingredients, including: -All plain grains - Corn flakes - Shredded wheat - Rice Krispies - Plain oats and oatmeal - Cream of Wheat - Puffed wheat - Puffed rice - Cream of rice • Plain crackers with allowed ingredients: - Grissol Melba Toast - RyVita - Rye Krisp - Wassa Crisp bread - Rice cakes - Rice crackers • Plain pasta • Pasta dishes with allowed ingredients |
• Bleached flour (benzoyl peroxide
is the bleaching agent) • Popcorn with artificial flavors • Manufactured rice entrees • Any baked product with restricted ingredients • Breakfast cereals with restricted additional ingredients such as artificial colors, flavors, and preservatives • Flavored instant oatmeal • All manufactured pasta meals in packages or cans |
|
| Vegetables | • All pure fresh and frozen
vegetables and their juices except those on the restricted list • Homemade salad dressings containing allowed ingredients, e.g., oil, garlic, and herbs |
• Eggplant (aubergine)
• Pumpkin • Sauerkraut • Spinach • Tomato • Avocado • Olives in vinegar or brine • Vegetable dishes with restricted ingredients • Most commercial salad dressings, including mayonnaise |
|
| Fruit | • Apple
• Banana • Figs • Guava • Kiwi • Longans • Lychees • Mango • Melons of all types, such as: - Cantaloupe (rock melon) - Honeydew - Watermelon • Passion fruit • Pear • Rhubarb • Starfruit • Fruit dishes, juices, jams, jellies, and conserves made with allowed fruits and ingredients |
• Apricot
• Blueberry • Cherry • Cranberry • Currant • Dates • Grapes • Loganberry • Nectarine • Orange • Grapefruit • Lemon • Lime • Mulberry • Papaya (pawpaw) • Peach • Pineapple • Prunes • Plums • Raisins • Raspberries • Strawberries • Fruit dishes, juices, jams, jellies and conserves made with restricted fruit and other ingredients |
|
| Meat, Poultry,
and Fish |
• All pure, freshly cooked meat
or poultry without restricted ingredients • Fresh fish if it has been caught, gutted, and cooked or frozen without delay |
• All fermented processed meats
such as - Salami - Bologna - Pepperoni - Weiners - Smoked or pickled meats -All leftover cooked meat • All shellfish • All fish, whether fresh, frozen, or canned, unless it has been freshly caught, gutted, and cooked without delay • Pickled fish • Smoked fish • Any meat, poultry, or fish made with restricted ingredients |
|
| Eggs | • Egg as a minor ingredient
in any allowed products (e.g., cakes, muffins, breads, and other baked goods) |
• Dishes in which egg is the
main ingredient, such as: - Souffle - Mousse - Quiche - Omelet • Scrambled, boiled, fried eggs • Egg dishes prepared with restricted foods • Raw egg white (as in eggnog, Hollandaise sauce, traditional Caesar salad dressing, mayonnaise, some milk shakes) |
|
| Legumes | • All plain legumes except
those on the restricted list • Pure peanut butter |
• Soy beans
• Red beans |
|
| Nuts and Seeds | • All plain nuts and seeds
except pumpkin seeds |
• Pumpkin seeds
• Any nut or seed mixtures with restricted ingredients (e.g., artificial barbecue flavor) |
|
| Spices and Herbs | • All fresh, frozen, or dried
herbs and spices except those on the restricted list |
• Anise
• Cinnamon • Cloves • Curry powder • Nutmeg • Seasoning packets with restricted ingredients • Foods labeled “with spices” |
|
| Fats and Oils | • Pure butter
• Pure vegetable oils • Homemade salad dressing with allowed ingredients • Lard and meat drippings • Homemade gravy |
• All fats and oils with color
and/or preservatives • Hydrolyzed lecithin • Margarine • Prepared salad dressings with restricted ingredients • Gravy made from mixes or in cans |
|
| Sweeteners | • Sugar, icing sugar
• Maple syrup, corn syrup • Honey • Jams, jellies, marmalade, and conserves made with allowed ingredients • Plain artificial sweeteners • Homemade sweets with allowed ingredients |
• Flavored syrups
• Prepared dessert fillings • Prepared icings/frostings • Spreads with restricted ingredients • Cake decorations • Commercial confectionery • Commercial candies |
|
| Beverages | • Plain milk
• Pure juices of allowed fruits and vegetables • Plain and carbonated mineral water • Coffee • Herbal teas made from allowed ingredients, without spices (no “zingers” or “zests”) |
• Flavored milks
• Fruit drinks and cocktails with restricted ingredients • Cola-type carbonated drinks • Flavored coffees • Tea, regular or green • All drinks with “flavor” or “spices” • All alcoholic beverages • “De-alcoholized” beers, wines, and other beverages |
|
| Other | • Baking powder
• Baking soda • Cream of Tartar • Plain gelatin • Homemade relishes with allowed ingredients |
• Chocolate and cocoa
• Flavored gelatin • Mincemeat • Prepared relishes • Olives • Soy sauce • Miso • Commercial ketchup • Pickles |
|
TYRAMINE SENSITIVITY
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