Histamine is a potent signaling molecule or biogenic amine made from the amino acid histidine. It is naturally found in plants and animals. Histamine helps regulate many bodily functions including digestion, sleep, sexual function, and blood pressure; and in the brain it functions as a neurotransmitter, carrying chemical messages between nerve cells. Under normal circumstances small amounts of histamine are helping to facilitate health and balance in many systems of the body. Large quantities of histamine are released in our bodies in response to foreign pathogens, wounds and allergies by mast cells, which are white blood cells that reside in tissues and basophils, which are white blood cells that reside in the blood. People with allergies often take antihistamine medications to provide relief of symptoms associated with this inflammatory response. Histamine exerts its effects by binding to four different receptor sites on target cells with each site producing different symptoms of various tissues and organ systems. (See diagram below) Antihistamine drugs do not destroy histamine and only block symptoms to the first site H1 so they are not effective at countering all symptoms.
Histamine is found in a variety of foods and when ingested is broken down by an enzyme called diamine oxidase of DAO, which is found in the lining of the small intestine and the upper end of the large intestine. Histamine in the central nervous system is broken down primarily by histamine N-methyltransferase (HMT). Some people have reduced DAO activity in their intestine so when they eat certain foods histamine and other biogenic amines are not broken down quickly and are absorbed into the body creating a condition called Histamine Intolerance. Excess amounts of histamine can cause a variety of symptoms including low blood pressure, headache, sleep disturbances, diarrhea, heart rhythm problems, acid reflex, hypertension, vertigo, anxiety, flushing, runny nose, asthma, hives, flushing, itchy skin, painful or irregular periods and fatigue. DAO is produced in very high concentrations by the placenta during pregnancy, and as a result women with Histamine Intolerance report a remission of symptoms when they are pregnant. There is also a relationship between estrogen and DAO levels, resulting in a decline in DAO levels and a worsening of the symptoms of histamine intolerance in perimenopausal and menopausal women.
Histamine Intolerance is often misdiagnosed as food allergies, eczema or Candida. It is however an IgG mediated response as opposed to an IgE response that occurs in allergies. The amount of histamine in a person fluctuates causing symptoms only when it is above a certain threshold. Symptoms are therefore dose-related, which is another important difference between histamine intolerance and allergies. The idea of histamine intolerance was initially researched in Germany in the 1980's. A Canadian Immunology PHD and dietician named Dr. Janice Joneja has also done a lot of research on this condition. Cited causes of low DAO levels include gastrointestinal conditions including Small Intestinal Bacterial Overgrowth (SIBO), Crohn's disease, gluten intolerance, ulcerative colitis and inflammatory bowel disease. The ingestion of alcohol and many medications can interfere with DAO activity. There is also some evidence that low levels of DAO and HMT may be inherited genetically. Dunwoody labs is currently the only laboratory that tests for DAO levels. The accuracy of their test has not been thoroughly validated and is based on studies performed on rats. Most experts agree that if one avoids foods that are high in histamine for a couple of weeks and the symptoms clear up, then it is likely that one has histamine intolerance.
Histamine levels are only known for some foods. Unfortunately there are lists of histamine releasing foods in articles on the Internet that are not based on objective scientific information rather on foods that people have reported reactions to. In general we know that alcohol (red wine has particularly high levels of histamine), fermented foods, black tea, cured meats, aged cheese, and ripe fruit and tomatoes, and many medications are high in histamine. Histamine is a byproduct of fermentation when bacteria or yeast are added to foods or when foods ages, ripens or spoils. The foods that individuals react to vary and sometimes a person can become increasingly intolerant to more and more foods. Along with avoiding foods high in histamine, taking a supplement that contains DAO obtained from pigs before each meal can be helpful. An Austrian company called Sciotech Diagnostic Laboratories (www.sciotec.at/en) is the only producer of DAO micropellets. They market a product called DAOsin in Europe and they sell micropellets to a few American companies that produce their own DAO supplements. Those companies include Swanson (DAOsin), Seeking Health (Histamine Block), and Xymogen (HistDAO). Not all people with Histamine Intolerance benefit from taking these supplements.
My particular food and drug sensitivities began at the onset of my health condition forty years ago. I suffered from chronic tension headaches, which I eventually resolved by doing EMG biofeedback training on the muscles in my neck and eliminating alcohol, caffeine (I drank black tea), drugs and sweets. Over the years I became increasingly sensitive to more and more foods eliminating citrus and dried fruits, soy sauce, aged cheese, cured and smoked meet and fish, and tomatoes. My reaction to these things is immediate beginning within several minutes of consuming them and lasts 24 hours during which time I have elevated muscle tension, feel uneasy, and have very disturbed sleep often with heat. I have never discovered an antidote to this reaction and simply have to ride it out, which can leave me exhausted afterwards taking several days to fully recover. Although there are some things that I can never consume without a reaction there are many that I can tolerate occasionally as my threshold is variable. I did not have these reactions when I was pregnant and my condition worsened as I approached menopause and has stayed about the same since that time.
My food and drug reactions do not correspond to any allergy testing whatsoever. In the early 90's I underwent a year of electrodermal allergy treatments at the Tahoma Clinic, then several years later I did a year of Nambudripad's Allergy Elimination Techniques (NAET) treatments, and more recently I tried Advanced Allergy Therapeutics. I experienced no improvement in my condition with these therapies. Last spring I discovered that I have Small Intestinal Bacterial Overgrowth and began treatments that have improved my digestion and overall health. I wrote a post about this last fall and received two independent responses from persons that have SIBO and also Histamine Intolerance, a condition I had never heard of. Looking into this subject I quickly realized that the foods and drugs I react to are high in histamine and that I have been on a low histamine diet for years as a way of managing it. My naturopathic physician ordered a test to measure my DAO levels from Dunwoody Labs, the results of which are still pending as the lab is revamping its procedures. I had a phone consultation with Wendy Busse, (www.HistamineReducingDiet.com) a Canadian nutritionist who worked closely with Dr. Janice Joneja. In terms of my particular reactions, Busse said that every person is unique however the fact that I am without symptoms when I adhere to my diet and that I did not have symptoms when I was pregnant is pretty strong evidence that I have Histamine Intolerance.
Two months ago I started taking 2-4 HIST DAO capsules before each meal. HIST DAO is manufactured by Xymogen (www.xymogen.com) and contains DAO micropellets and a small amount of ascorbic acid (vitamin C), which is an antihistamine. Taking these supplements has not allowed me to expand my diet but it seems like when I have a reaction it is less severe. and I have not become sensitive to additional foods. Additionally my sleep, which is typically light and disturbed is better. When taking the DAO supplement before each meal I experience some longer stretches (3-4) hours of deep sleep most nights. This is most likely due to the fact that histamine is a neurotransmitter associated with wakefulness.
There is some discrepancy about when exactly when to take DAO supplements. Some manufacturer says "right" before a meal, some say "withing 15 minutes", and according to a researcher at Sciotech laboratories who talked to Wendy Busse "15-30 minutes" before a meal. This discrepancy is due to the fact that there are variations in how long it takes the capsules to break down depending on the amount of stomach acid a person has. My solution for dealing with this is to put 2 capsules in my mouth right before each meal and let my saliva break down the capsules, then I swallow. The pellets have no particular taste.
It appears that Histamine Intolerance and Small Intestine Bacterial Overgrowth are overlapping conditions. This makes sense because DAO is produced in the lining of the small intestine, which is also the location of the bacterial overgrowth. There are a number of studies that show an increase in the activity of mast cells in persons with fibromyalgia and chronic fatigue syndrome. (http://phoenixrising.me/archives/13083) I think that histamine intolerance may play a role in sleep disturbances in persons with CFS & FMS because histamine is known to modulate sleep and histamine releasing neurons produce a wakefulness firing pattern. The research on histamine intolerance and its connection with other health conditions is preliminary at best however I think that this is a key player for many persons with CFS and FMS. An experimental trial on a low histamine diet and then taking DAO supplements before meals is a reasonable approach as it may yield improvements in one's health.
P.S. After many months of waiting Dunwoody Labs finally began running tests for Diamine Oxidase (DAO) and Histamine. My levels of DAO were extremely low and the ratio between DAO and Histamine was well out of the normal reference range.