On October 23rd the magazine SABER VIVIR tve published an article about the DAO deficiency, its causes and management called “Migraine, itching, stomach pain… This is how DAO deficiency affects you”.
It is signed by the journalist specialized in health Eva Mimbrero and has the advice of the allergist Dr. Pedro Ojeda, co-director of the clinic Ojeda of Asthma and Allergy and a member of the International Society of Deficit of DAO.
To access the original article click here clic here.
What is histamine?
The article begins by explaining what the histamine molecule is, what its sources are in the organism (since it is produced and stored in certain cells, and can also be acquired through food in the case of a deficit of DAO) and what physiological functions it performs, among which are the secretion of gastric juices, processes of the immune system, neurotransmission in the nervous system, among others.
Which systems are affected?
After introducing the role of histamine in the body, the deficit of DAO and its symptoms are discussed. This consists of an alteration in the metabolism of histamine that comes from food, this alteration being caused by the deficit of the enzyme Diamino Oxidase.
Among its symptoms at the neurological level is migraine (87% of people who suffer from migraine have a deficit of DAO, according to a clinical study conducted in Spain), at the skin level itching, redness, emergence of beans, hives and angioedema, at intestinal level gastric pain, cramps, gas or diarrhea, at gynecological level menstrual pain, at cardiac level palpitations, arrhythmias or tachycardias, and at respiratory level rhinitis and the feeling that it is difficult to breathe.
Which are the causes?
Before going on to talk about methods for the dietary management of the symptoms of DAO deficiency, it is emphasized that DAO deficiency is not an allergic response but that its effects and control are more prolonged over time, being more durable and less instantaneous processes.
Finally, the article identifies the main causes of DAO deficiency, among which are the genetic alteration in the individual’s DAO enzyme, certain inflammatory intestinal disorders that alter the intestinal mucosa where DAO is produced (such as celiac disease, Crohn’s disease or ulcerative colitis), the consumption of certain drugs that inhibit the enzyme, or the consumption of alcoholic beverages, since alcohol also acts as a potent inhibitor of the enzyme.
How to handle it?
Once these causes have been identified, it ends up talking about the management of the symptoms, in which its three fundamental pillars are the diagnosis of the specific cause in each patient, avoiding the consumption of alcohol and certain foods rich in histamine, as well as keeping a medical control of the drugs that are consumed, and finally following a dietary supplementation of diamond oxidase.
To access the original article click here clic here.
Associations Between Migraine, Celiac Disease, Non-Celiac Gluten Sensitivity and Activity of Diamine Oxidase
Background and pilot study: Recent reports reveal a close relationship between migraine and gastrointestinal disorders (GI), such as celiac disease (CD) and non-celiac gluten sensitivity (NCGS). CD is a genetic autoimmune disorder, which affects the mucosa of the small intestine. Gluten, found in various grains, not only plays a major role in the pathophysiology of CD and NCGS, but also aggravates migraine attacks. Another common food component, which can induce migraine headaches, is histamine. Diamine oxidase (DAO) is an enzyme, which degrades histamine. Reduced activity of DAO means reduced histamine degradation, which can cause histamine build-up and lead to various symptoms, including headaches and migraine. In this paper we propose a hypothesis, that in pathogenesis of migraine, low serum DAO activity is related to CD and NCGS. We also conducted our own pilot study of 44 patients with severe migraine in efforts to evaluate the co-presence of decreased serum DAO activity and celiac disease/NCGS in patients. 44 consecutive migraine patients were divided into 2 groups: decreased DAO activity (group 1; n = 26) and normal DAO activity (group 2; n = 18). All patients were screened for celiac disease. The diagnosis of NCGS was made after exclusion of CD, food allergies and other GI disorders in the presence of gluten sensitivity symptoms. Furthermore, dietary recommendations were given to all participants and their effects were assessed 3 months after the initial evaluation via the MIDAS (Migraine Disability Assessment) questionnaire.
Results and conclusions: Only 1 patient fit the criteria for celiac disease, rendering this result inconclusive. Pathological findings of the remainder of patients were attributed to NCGS (n = 10). 9 of 10 patients with NCGS belonged to the decreased serum DAO activity group (group 1; n = 26), suggesting a strong relationship between reduced serum DAO activity and NCGS. MIDAS questionnaire revealed, that patients with decreased serum DAO activity were more severely impacted by migraine than those with normal DAO activity, and this remained so after our interventions. Dietary adjustments significantly reduced the impact of migraine on patients’ daily activities after 3 months in both groups. We argue, that migraine, celiac disease and NCGS may benefit from treatment with a multidisciplinary approach, involving neurologists, gastroenterologists and dietitians.
We live in a time of real uncertainty with the worldwide spread of COVID-19 and anxiety levels are high. It is important to remain calm, listen and apply the advice of the Health Authority.
Considering that the activities of DR Healthcare are focused on the study of histamine, DAO deficiency and histamine intolerance, it is worth mentioning recent publications that support the fact that mast cell activation and histamine release can contribute to the inflammation associated with SARS COV-2 infection (new strain of coronavirus that causes COVID-19) .
Coronavirus infection (regardless of the various types of coronavirus) is primarily attacked by immune cells, including mast cells (MC), which are found in the submucosa of the respiratory tract and in the nasal cavity, representing a protective barrier against microorganisms. Viruses activate mast cells that release early inflammatory chemical compounds such as histamine and protease (1). In people with DAO deficiency who, due to this condition, have high levels of circulating histamine, a greater histamine accumulation caused by the aforementioned virus-activated mastocytosis, may aggravate the inflammatory process generated by the infection.
Under normal conditions, when histamine levels rise above a certain threshold, the enzymes responsible for its metabolism, specifically DAO (Diamino Oxidase) and, to a lesser extent, histamine N-methyl transferase (HNMT), rapidly degrade the excess this amine. However, when the degradation rate is insufficient to cope with the excess, the total level of histamine in the body rises. At a certain critical level, signs and symptoms occur as a result of histamine coupling to its receptors in specific cells.
Histamine is a mediator that intervenes in the inflammation of the immune system by activating intracellular pathways that induce the production of cytokines in the lungs. Cytokines are signaling proteins that regulate interactions of cells of the immune system, thus producing an amplification of inflammatory reactions.
Based on the aforementioned studies and the pathophysiology of the disease, it is important to maximize the basic recommendations to protect against COVID-19, avoiding an accumulation of histamine in people with DAO deficiency and / or mastocytosis. Since inflammation is a concern in the severity of the disease caused by SARS COV-2, it is recommended to reduce the consumption of foods high in histamine in the diet and take supplements that allow maintaining a balance between endogenous and exogenous histamine, avoiding an excess of histamine in the body, and therefore reducing the mast cell / histamine load.
Thus, in addition to the basic general guidelines to prevent the spread of COVID-19 in the entire population, there are a number of added recommendations to consider in people with DAO deficiency and / or intolerance to histamine:
-Avoid eating foods with a high concentration of histamine or other biogenic amines that compete for the DAO enzyme. These include, for example, raw, pasteurized milk and dairy products; citrus, strawberries and banana; seafood, blue fish and fish sauces; the raw sausage, such as sausage, chorizo or bacon; some vegetables, such as tomato, spinach or eggplant, as well as alcoholic beverages.
-Oral supply of DAO enzyme to prevent systemic absorption of exogenous or dietary histamine. This facilitates the metabolism of food histamine locally in the small intestine, restoring the natural balance of histamine and DAO.
–DAOfood® Plus contains the DAO enzyme that complements the body’s own enzyme and increases the degradation capacity of exogenous histamine. It also contains Quercetin that acts as an adjuvant against endogenous histamine. Its intake prevents the absorption and accumulation of circulating histamine and therefore counteracts the release of endogenous histamine as a reaction of the body when it comes into contact with the virus.
It is important to note that because SARS COV-2 is classified as a new strain of coronavirus, there is limited scientific evidence available on its precise mode of action and infection. Therefore, what is indicated in this article is based on what we know so far and on the importance of protecting against the virus, while maintaining control of mastocytosis and DAO deficiency.
The DR Healthcare team is at your entire disposal in case of concern about the implications of COVID-19 in people with DAO deficiency.
1.- Kritas, S. K., Ronconi, G., Caraffa, A., Gallenga, C. E., Ross, R., & Conti, P. (2020). Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. Journal of biological regulators and homeostatic agents, 34(1), 10.23812/20-Editorial-Kritas.
Given the difficult scenario that we are facing caused by the Coronavirus pandemic in general and after the State of Alarm decreed by the Spanish government in particular, DR Healthcare has implemented a safety and business continuity protocol that guarantees the provision of our services, the supply of the active ingredient, and, safeguard the health of all our collaborators and customers.
In this sense, we want to indicate that:
• The staff in the areas of administration, customer service and patient care operate in telework mode to meet themobility and contact requirements, guaranteeing the maintenance of their normal operation and service.
• Laboratory and R&D personnel who cannot carry out their activity remotely, following the security protocol, have established rotating work shifts to avoid human contact.
• The staff of the enzyme production plant has also implemented an intensive schedule protocol with rotating shifts that prevents human contact andensures non-interruption of the DAO enzyme production process.
Likewise, our suppliers and logistics network have adapted their processes to the current situation, ensuringthe safety and continuity of the supply chain of both the active ingredient and finished products up to the final customer, whether national or international.
We thus contribute to the containment of the disease and comply with the measures required by the competent authorities, guaranteeing our best service.
The DR Healthcare team is at your disposal for any additional information you may require.
CEO DR Healthcare
You can download the supplement in pdf clicking in the image below or through here. (LANGUAGE: SPANISH)
el farmacéutico.es publishes its supplement nº 585 entitled “Migraine and DAO deficiency (Diamine Oxidase)”.
In this publication the scientific and clinical bases of migraine caused by DAO deficiency are exposed and the diagnostic methods and forms of migraine management caused by this metabolic alteration are shown. Products that can be found in pharmacies for the management and diagnosis of migraine caused by DAO deficiency are also shown.
The supplement has been prepared by the PhD. Medical Writer Antoni X. Torres-Collado and Eva Morán-Salvador, edited by MAYO editions and published on March 2 – 2020.
Contents of supplement nº585 “Migraine and DAO deficiency (Diamine Oxidase)”:
- What is migraine?
2. Symptomatology and diagnosis
3. Management and treatment of migraine
- What happens in migraine?
1. Phases of the migraine crisis
2. Phystopathological mechanisms
3. What is histamine?
- What is Diamino Oxidase?
- DAO and migraine deficit
1. pregnancy and migraine
2. associated symptoms (migraine comorbidity)
4. Management of Migraine due to DAO deficiency
- How to manage migraine due to DAO deficiency from the pharmacy?
1. DAO supplementation in the patient with migraine: food for special medical uses
Publication of the article “Do you know the difference between DAOfood and Migrasin? In the blog about health and wellness tips, novel and natural beauty treatments dosfarma.com. Language: Spanish.
This paper informatively discusses the role of food histamine and the enzyme diamino oxidase (DAO) in DAO deficiency and its associated pathologies. It also shows us how the DR Healthcare company is one of the pioneer companies in the investigation of this widespread metabolic disorder and informs us of the composition and indications of its DAOfood and Migrasin products. So, if you don’t know the differences between DAOfood and Migrasin, this article will show you what to take in each moment properly.
DAOfood is indicated for the treatment and prevention of gastrointestinal, cutaneous and muscular disorders and pathologies. Being its main component the enzyme diamino oxidase (DAO).
Migrasin, containing DAO enzyme, group B vitamins (B6, B9 and B12) and caffeine, is indicated for the treatment and prevention of migraine and muscle headaches.
To access the article in dosfarma.com click here.
Association of Diamine oxidase (DAO) variants with the risk for migraine from North Indian population
Association of Diamine oxidase (DAO) variants with the risk for migraine from North Indian population
Sukhvinder Kaura,⁎, Arif Alib, Yaser Siahbalaeic, Uzair Ahmadc, Fazila Nargisc, A.K. Pandeyd,
a UGC-PDF, Gene Expression Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
b UGC-BSR-FF, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
c Department of Biosciences, Jamia Millia Islamia, New Delhi, India
d Head, Department of Physiology, ESIC Medical College & Hospital, Faridabad, India
e NC Medical College & Hospital, Panipat, India
A B S T R A C T
Background: Migraine is a common neurovascular disorder affected by various levels of neurotransmitters. Low histamine metabolism is also related with pathophysiology of migraine. As diamine oxidase (DAO) gene variants are linked with higher levels of histamine in migraine patients, we investigated the possible relationship of two variants rs2052129 and rs10156191of this gene with migraine risk in North Indian population.
Methods: A case-control study for 250 migraine patients and 250 matched healthy controls was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results: We found statistically significant differences in allelic frequencies of rs2052129 (p = .009, OR = 1.462; 95% CI: 1.098–1.947) and rs10156191 (p = .019, OR = 1.430; 95% CI: 1.060–1.928) variants in DAO gene. For rs1015691, we were able to show statistically significant association at all genotypic, dominant and allelic levels in both MA (for T allele, p = .020; OR = 1.662, 95% CI: 1.083–2.551) as well as in female subgroup (for T allele, p = .025, OR = 1.460; 95% CI: 1.049–2.033). But no such significant association was found in clinical sub grouping of migraine in rs2052129 as p > .05. However in gender analysis, protective effect of T allele in male migraine patients for rs2052129 (OR < 1) was found.
Conclusions: Our findings clearly indicated that female patient with rs10156191T allele and in MA subgroup showed an increased risk for migraine. Our data also indicated that rs2052129T variant showed a significant role in migraine susceptibility of this population.
Impaired resolution of wheals in the skin prick test and low diamine oxidase blood level in allergic patients
Aneta Wagner1, Krzysztof Buczyłko2, Hanna Zielińska-Bliźniewska1, Waldemar Wagner3
1Allergology and Respiratory Rehabilitation Department, Medical University of Lodz, Lodz, Poland
2NZOZ Allergology Center, Lodz, Poland
3Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland
Adv Dermatol Allergol 2019; XXXVI (5): 538–543
Introduction: Histamine is the major mediator of IgE- and non-IgE-mediated allergic reactions upon allergen or
hapten contact. Reduced histamine degradation capacity was associated with atopic eczema as well as with nonimmunological
histamine intolerance. Higher blood serum histamine level concomitant with decreased intestinal
diamine oxidase activity were observed in patients with food allergy.
Aim: To evaluate the relationship between patients’ blood diamine oxidase (DAO) activity/histamine status and
their reactivity to time-resolved histamine skin prick test in respect to vulnerability to allergic diseases.
Material and methods: Fifty-three patients were examined with skin prick tests (SPT) and patch tests for suspected
presence of either IgE- or non-IgE-mediated allergy. All individuals were skin prick tested with histamine and the
resolution of the wheal was monitored for 50 min. Blood DAO activity and histamine concentration were measured
with a radio-extraction radioimmunoassay.
Results: Time-resolved histamine skin prick testing revealed presence of wheals which were 35% larger in diameter
in 47% of examined subjects at 20 min of the test. These patients exhibited significantly compromised time-course
wheal resolution (wheal ≥ 3 mm at 50 min) compared to a group of patients with the normal-rate of wheal resolution
(wheal = 0 mm at 50 min). Within a group of subjects exhibiting impaired wheal resolution, 61% of patients
were diagnosed allergic compared to 50% in a group of patients with a normal rate of wheal resolution. Finally,
allergic patients were characterized by a significantly lower DAO activity and higher histamine content compared
to healthy subjects.
Conclusions: The results of this study indicate that patients with IgE- or non-IgE-mediated allergy are likely to
have low DAO blood activity and may concomitantly suffer from histamine intolerance. Furthermore, our results
suggest that allergic patients are more likely to develop an excessive SPT reaction. Our results emphasize caution
in interpretation of the SPT results in allergic patients with diagnosed histamine intolerance or histamine/DAO
The past 20 May was published in the European Journal of Neurology an article in which the doctors Wolfgang J Schnedl and Robert Queissner stated that there was apparently a greater relationship between the cause of migraines and histamine rather than with ethanol present in alcoholic beverages.
In the letter to the editor that have published both doctors, reflect on another recent publication of Onderwater et al, in the same magazine, in which it is intended to show by epidemiological studies a causal relationship between ethanol of alcoholic beverages and the development of migraines in people who consume.
However, both doctors argue that no one has been identified as specific pathophysiologic mechanism that correlate the alcohol intake with migraines and headaches (being the red wine the alcoholic beverage that has been related in the study population of Onderwater et al with migraine).
They argue, in contrast, that greater evidence exists so far as a cause of migraines and headaches are the deficit of the enzyme diamine oxidase (DAO) (alteration in the main route of metabolism of dietary histamine and can be present as a heritable genetic alteration) and the effects that generate exogenous histamine and other biogenic amines (such as tyramine, phenylethylamine, putrescine, cadaverine, spermidine, serotonin, tryptamine, agmatin) when they accumulate in plasma after being ingested.
The results of measurement of these amines into alcoholic beverages show that has been quantified higher concentrations in red wine (with concentrations >2,200 μg/L), being double the concentration that can be found in the white wine ( ~900 μg/L), and much higher even than in distilled spirits such as vozka. This difference in concentration also has been related to a lower incidence of migraine in studies in which the population consumed vozka than in the population that consumed wine.
With regard to the pathophysiologic mechanism of the cause of migraines by DAO deficiency, certain genotypes of the enzyme DAO and its allelic variants (all of them involved in a deficit of the enzyme activity) have shown association with increased risk of migraine. On the other hand, recent studies consisting of double-blind randomized trials in which a population of migraine patients were treated with supplements of DAO, have shown a reduction in the number, frequency, and intensity of migraines. States of these results, other studies of supplementation with DAO on patient population with intolerance to histamine (HIT), has shown a reduction of headaches and the rest of the symptoms related to this pathology.
Outside the interest and data and studies shown about people affected with a diagnosis of DAO deficiency and intolerance to histamine, this letter to the editor does not mention the inhibitory role of ethanol on the activity of the diamine oxidase, which explains the syndrome of the hangover after the acute intake of alcohol in people without a diagnosis of HIT or DAO deficiency.
Dr. Wolfgang J Schnedl is professor of internal medicine and doctor in the General Internal Medicine Practice Theodor Könerstrasse (Austria), and Dr. Robert Queissner is a professor in the Department of Psychiatry and Psychotherapeutic Medicine of the Medical University of Graz (Austria).
Next Monday 17 June (2019), will take place from 14.00 to 16.00 hours in the University Rovira i Virgili (Edifici N5 Sustainable Chemistry, Assembly Hall.Marcel.li Sunday, 2-4-6, Sescelades Campus 43007-Tarragona, Spain) the training activity “DAO deficiency and the role of the pharmacist in the diagnosis and treatment” (language: Spanish).
This training is organized by DR Healthcare, Spanish biomedical company leader in research and development in deficit of DAO, by the Col·legi Oficial de Farmacèutics of Tarragona and by the University Rovira i Virgili (URV), and endorsed by the International Society of DAO Deficiency, maximum scientific authority at the international level in DAO Deficiency.
It is a free training and in which you can obtain a certificate of attendance issued by the International Society of DAO Deficiency.
The training focuses on the role of the pharmacist in the diagnosis and treatment of the DAO deficiency, as it is a metabolic alteration that affects a 16% of the population and is involved in the cause of chronic diseases highly disabling as migraine, fibromyalgia and irritable bowel, as well as a wide range of neurological, dermatological, rheumatologic and gastrointestinal disorders.
Below shows the programming and the speakers of the training.
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