277 | id == 277
277 | category_id == 19
277 | category_order == 16
277 | category_name == Pain
277 | category_color == #C47AC0
277 | slug == DAO-pain
277 | title == Is Excess Histamine Causing Your Migraines? (DAO)
277 | meta_description == Diamine oxidase (DAO) is the main enzyme that breaks down histamine in the gut. Could high histamine be causing your migraines?
277 | summary == <p><strong>Diamine oxidase (DAO) is the main enzyme that breaks down histamine in the gut. Could high histamine be causing your migraines? Learn more here.</strong></p>
277 | overall_score_text == Migraine Score (based on DAO)
277 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/DAO--Pain-Headaches-Migraine.jpg
277 | author_id == 1
277 | author_name == Jasmine Foster
277 | author_title == BSc, BEd
277 | author_order == 36
277 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Jasmine.jpg
277 | author_intro == <p><strong>Jasmine received her BS from McGill University and her BEd from Vancouver Island University.</strong></p>    <p>Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.</p>
277 | reviewer_id == 14
277 | reviewer_name == Shany Lahan
277 | reviewer_title == MS (Neuroscience)
277 | medical_reviewer_id == 11
277 | medical_reviewer_name == Puya Yazdi
277 | medical_reviewer_title == MD
277 | publish_date == 2020
277 | publish_date == 8
277 | publish_date == 17
277 | avg_rating == 5.0
277 | tags_id == 25
277 | tags_name == DAO
277 | tags_id == 623
277 | tags_name == Histamine
277 | tags_id == 22
277 | tags_name == Histamine Intolerance
277 | tags_id == 31
277 | tags_name == Migraine
277 | permissions_favorite == False
277 | permissions_rate == False
277 | content_article == <p><em><span style="font-weight: 400;">If you have persistent or unexplained pain, it is important to discuss these concerns with your doctor. The information in this post is presented for educational purposes only, and should not be used to replace standard medical care.</span></em></p> <h2><span style="font-weight: 400;">What is DAO</span></h2> <p><span style="font-weight: 400;">The </span><a href="../../../gene/aoc1/"><em><span style="font-weight: 400;">DAO</span></em></a><span style="font-weight: 400;"> gene encodes diamine oxidase (also abbreviated DAO), the primary enzyme that breaks down histamine in the digestive system [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17490952"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Histamine is a biogenic amine: that is, a compound made in your body that includes an amine group. Histamine is not the only biogenic amine, but it is the best-known and best-studied because it triggers inflammation, itchiness, and pain [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485016/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24286351"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604636/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29371440"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Histamine was discovered in 1910 by the winner of the 1936 Nobel Prize in Medicine, Sir Henry H. Dale. Its name is derived from the Greek word histos, meaning tissue, as many tissues throughout the body express it [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822965/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24286351"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Two enzymes control histamine breakdown: histamine N-methyltransferase (</span><a href="../../article/brain-histamine-hnmt-13"><span style="font-weight: 400;">HNMT</span></a><span style="font-weight: 400;">) and DAO. These enzymes are extremely important. If either one starts malfunctioning, histamine can increase dramatically throughout the body [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068859/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24286351"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">DAO is an enzyme that breaks down histamine, a compound that stimulates inflammation, itchiness, and pain.</span></p> <h2><span style="font-weight: 400;">DAO &amp; Histamine Intolerance</span></h2> <p><span style="font-weight: 400;">Histamine intolerance is something of a misnomer; it isn&rsquo;t really a sensitivity to histamine. Rather, people with histamine intolerance have too much histamine: they either create it in excess or they can&rsquo;t break it down quickly enough due to abnormally low levels of DAO, HNMT, or both [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17490952"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">When people with low DAO eat foods that contain histamine, histamine crosses into their blood, and they experience inflammation. Someone with normal levels of DAO would break down most dietary histamine before it ever reaches the bloodstream [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17490952"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24286351"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In many ways, histamine intolerance mimics an allergic reaction. Symptoms may include diarrhea, </span><a href="https://selfhacked.com/blog/natural-treatment-migraines/"><span style="font-weight: 400;">headaches</span></a><span style="font-weight: 400;">, stuffy and runny nose, eye redness, asthma, low blood pressure, arrhythmia, hives, itching, and flushing [</span><a href="http://onlinelibrary.wiley.com/doi/10.1111/all.12330/full"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Approximately 1% of the population has symptoms consistent with histamine intolerance. In contrast to food allergies, in which even a small amount of the allergen causes a reaction, the cumulative amount of histamine is crucial to inducing a reaction [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17490952"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Does Histamine Cause Migraines?</span></h3> <p><span style="font-weight: 400;">Histamine causes </span><a href="http://selfhacked.com/blog/natural-treatment-migraines/"><span style="font-weight: 400;">headaches</span></a><span style="font-weight: 400;"> by triggering the release of nitric oxide and increasing inflammation. It can induce headaches in healthy people as well as in those with migraine [</span><a href="http://ajcn.nutrition.org/content/85/5/1185.long"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Many migraine patients have histamine intolerance, reduced DAO activity, and elevated histamine during both attacks and symptom-free periods. Food rich in histamine triggers headaches, while a histamine-free diet and therapy with antihistamines alleviate headaches in these people [</span><a href="http://ajcn.nutrition.org/content/85/5/1185.long"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">People with low DAO enzyme activity may be susceptible to allergy-like symptoms, headaches, or migraines if they are exposed to high levels of histamine.</span></p> <h2><span style="font-weight: 400;">DAO Variants &amp; Migraine</span></h2> <p><span style="font-weight: 400;">Four </span><em><span style="font-weight: 400;">DAO </span></em><span style="font-weight: 400;">variants have been associated with lower levels of the DAO enzyme and higher incidence of migraine: rs1049793, rs2052129, rs10156191, and rs1049742 [</span><a href="https://pubmed.ncbi.nlm.nih.gov/25612138/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21488903/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/27130307/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In almost every case, the minor allele reduces DAO activity, possibly by producing a non-functional or less-functional version of the enzyme. Lower DAO enzyme activity reduces the body&rsquo;s capacity to break down and deactivate histamine, potentially leading to inflammation and pain [</span><a href="https://pubmed.ncbi.nlm.nih.gov/25612138/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21488903/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/27130307/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The exception to the rule is rs2052129, at which the minor &lsquo;T&rsquo; allele seems to be protective against migraines, but only in men. In women, there was no statistical difference between any genotype. Don&rsquo;t forget to take this difference into account in your SNP table [</span><a href="https://pubmed.ncbi.nlm.nih.gov/25612138/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]!</span></p> <h2><span style="font-weight: 400;">Your DAO Results for Migraine</span></h2> <p>*3087064586454071*</p> <h3><span style="font-weight: 400;">SNP Summary and Table</span></h3> <p><strong>DAO rs1049793</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Associated with normal levels of DAO</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Associated with reduced levels of DAO and possibly increased incidence of migraine</span></li> </ul> <p><strong>DAO rs2052129</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Associated with normal levels of DAO</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with increased levels of DAO, possibly protective against migraine in men only</span></li> </ul> <p><strong>DAO rs10156191</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Associated with normal levels of DAO</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with reduced levels of DAO and possibly increased incidence of migraine</span></li> </ul> <p><strong>DAO rs1049742</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Associated with normal levels of DAO</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with reduced levels of DAO and possibly increased incidence of migraine</span></li> </ul> <p>*4033491702660998*</p> <h2><span style="font-weight: 400;">Recommendations to [Improve Phenotype]</span></h2> <p>*7985970703552823*</p> <h3><span style="font-weight: 400;">Diet</span></h3> <h4><span style="font-weight: 400;">Low Histamine Diet</span></h4> <p><span style="font-weight: 400;">Histamine is a well-known cause of headaches and a possible culprit behind some people&rsquo;s</span><a href="https://selfhacked.com/blog/natural-treatment-migraines/"><span style="font-weight: 400;"> migraines</span></a><span style="font-weight: 400;">. Some researchers suspect type 3 and 4 histamine receptors are responsible for migraines, but specific studies are lacking [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17490952"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24433203"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30909864"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">One study found that a diet low in biogenic amines improved chronic headaches in 73% of patients. In this same study, histamine-rich foods were reintroduced and reliably caused headaches to occur again [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10779289"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604636/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">For a more detailed look at foods that are high and low in histamine, </span><a href="https://selfhacked.com/blog/foods-high-low-in-histamine/"><span style="font-weight: 400;">check out this post</span></a><span style="font-weight: 400;">.</span></p> <h4><span style="font-weight: 400;">Limit Alcohol Consumption</span></h4> <p><span style="font-weight: 400;">Alcohol triggers the release of histamine from white blood cells, inhibits DAO activity, and may change histamine metabolism in other ways. As little as one or two drinks is believed to be enough to trigger these effects [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10344773"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">About one third of migraine patients report alcohol as an occasional migraine trigger. However, other evidence suggests that alcohol in some forms and in small quantities may actually be beneficial to migraine patients, but more research is needed [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3476173/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21336550/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Doctors strongly recommend against binge drinking or heavy drinking for general health. Even if you don&rsquo;t think that alcohol is a migraine trigger, it&rsquo;s always a good idea to moderate your consumption of alcohol [</span><a href="https://pubmed.ncbi.nlm.nih.gov/21336550/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">People with low DAO activity may wish to cut down on alcohol consumption and avoid foods with high histamine levels.</span></p> <h3><span style="font-weight: 400;">Supplements</span></h3> <h4><span style="font-weight: 400;">Palmitoylethanolamide</span></h4> <p><a href="https://selfhacked.com/blog/palmitoylethanolamide-pea/"><span style="font-weight: 400;">Palmitoylethanolamide</span></a><span style="font-weight: 400;">, or </span><a href="https://selfhacked.com/blog/palmitoylethanolamide-pea/"><span style="font-weight: 400;">PEA</span></a><span style="font-weight: 400;">, is a fatty acid already found in your body. PEA is best known for its potential as a natural painkiller, but it also prevents histamine release from white blood cells [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429331/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Limited studies are available on PEA for migraine, though the existing evidence is promising. One study of 70 children with migraines found that PEA reduced both the number and intensity of migraines over three months; only one patient reported mild side effects [</span><a href="https://www.hindawi.com/journals/prm/2020/3938640/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957685/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A decent amount of evidence backs up PEA&rsquo;s ability to reduce other types of pain as well. It has been investigated in over 30 clinical trials and a total of about 6,000 people since the 1970s [</span><a href="https://pubmed.ncbi.nlm.nih.gov/22845893/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Many animals and plants also produce PEA. The highest amounts can be found in soy lecithin, soybeans, egg yolk, peanuts, and alfalfa. PEA activates the anti-inflammatory </span><a href="https://selfhacked.com/blog/about-ppar-alpha-and-natural-ways-to-activate-it/"><span style="font-weight: 400;">PPAR alpha</span></a><span style="font-weight: 400;"> while reducing the activity of the </span><a href="http://selfhacked.com/blog/the-bliss-gene-faah-snps-rs324420/"><em><span style="font-weight: 400;">FAAH</span></em></a> <span style="font-weight: 400;">gene. FAAH breaks down the calming cannabinoid anandamide [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429331/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><span style="font-weight: 400;">SAM-e</span></h4> <p><span style="font-weight: 400;">SAM-e (</span><a href="https://selfhacked.com/blog/s-adenosyl-l-methionine/"><span style="font-weight: 400;">S-Adenosyl-L-methionine</span></a><span style="font-weight: 400;"> or AdoMet) occurs naturally in the human body. As a supplier of a methyl group and organic sulfur, SAM-e drives complex metabolic reactions that control cell growth and life cycle, inflammation, brain chemistry, and more [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12418493/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23661436"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Some research suggests that SAM-e might support the function of HNMT, the other major enzyme that breaks down histamine. It may also reduce the amount of new histamine that is produced by the body [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12418493/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/gene/3176"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/4083177"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Decades-old evidence suggests that SAM-e can reduce the frequency and intensity of migraines, but only if it is supplemented over a long period of time. SAM-e is not typically prescribed for migraines, and these studies have not been repeated in a long time, so caution is recommended [</span><a href="https://pubmed.ncbi.nlm.nih.gov/3514492/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">PEA and SAM-e have produced promising results in early clinical migraine trials, but more research is required.</span></p>
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277 | content_learn_more_4033491702660998_text == Based on the variants we looked at, your DAO gene is associated with slightly lower than normal enzyme activity and higher histamine levels. However, this doesn't necessarily reflect your overall risk of migraine, just one gene related to it. Limiting alcohol consumption, eating low histamine foods, and choosing some antihistamine supplements may help. Keep scrolling to find out more.
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rsIDs = rs10156191,rs324420,rs2052129,rs1049742,rs1049793
rsStatus = rs10156191,AOC1,chr7,150856517,C,T,,,28,0,Normal
rsStatus = rs324420,FAAH,chr1,46405089,C,A,,,20,13,HET
rsStatus = rs2052129,AOC1,chr7,150851884,G,A,T,,36,0,Normal
rsStatus = rs1049742,AOC1,chr7,150857465,C,T,,,30,1,HET
rsStatus = rs1049793,AOC1,chr7,150860577,C,G,T,,30,0,Normal
