Migraines and headaches associated with DAO Deficiency

Migraine is a neurological disease characterized by the recurrent presence of intense and disabling headaches, which are usually unilateral and pulsating. Along with headache, the most common symptoms are nausea, vomiting, sensitivity to light and sound. Migraine affects around 12% of the population, being more prevalent in women of childbearing age, with an incidence of up to 25%. The WHO considers migraine to be the second most disabling human disease, with a disease burden comparable to blindness or paraplegia. There is evidence to suggest that hormonal changes may influence the frequency and intensity of seizures, but today it is known that deficiency of the enzyme Diamine Oxidase (DAO) may also play a relevant role in the appearance of migraines and other Headaches.

Cluster headache , also called Horton's Headache or Cluster Headache, is a vascular condition that causes intense and recurring pain, mainly on one side of the head. The attacks usually last from 15 to 180 minutes and can occur several times a day, for days or weeks. In addition to pain, other symptoms such as tearing, nasal congestion, sweating, and agitation may occur. Men are more likely to have this condition than women, and the age of onset is typically between the ages of 20 and 40. Approximately 90% of patients experience periods of remission between attacks, although a minority suffer from chronic cluster headache without periods of remission.

The pathophysiology of migraine involves several systems and mechanisms in the peripheral and central nervous system. In the trigeminal vascular system, the meningeal vessels are surrounded by sensory fibers from the trigeminal nerve and, when activated, cause sterile meningeal inflammation and pain. Although no specific lesion has been found to cause migraine, a genetic component and possible mutations in the DAO gene have been identified. In addition, various neuromodulators and substances such as histamine have been linked to the pathophysiology of migraine.

What is the role of histamine and DAO deficiency in migraine?

In summary, histamine is a biogenic amine present in the body and in many foods, and is involved in processes such as neuromodulation, vascular regulation, and allergic reactions. Excess histamine in the body, either due to an excessive intake of foods rich in histamine or a defect in its breakdown, can be related to various pathologies, including migraine and headaches. Histamine can also trigger acute headaches in some people, as classified by the Headache Classification Committee of the International Headache Society. The enzyme diamine oxidase (DAO) is responsible for the breakdown of histamine in the body, and a deficit in its activity can lead to the accumulation of histamine and the appearance of migraine symptoms.

In the diagnosis of migraine, no method based on complementary tests such as resonances or analysis is used. The diagnosis is made mainly through clinical criteria established by the International Headache Society (IHS), which are accepted worldwide by neurological societies. The IHS classifies migraine into two main subgroups: migraine without aura and migraine with aura. However, recently it has been found that the activity of the DAO enzyme may be an important biomarker in the diagnosis of migraine and other headaches.

What is migraine without aura?

Migraine without aura is a recurring disease that causes headaches lasting between 4 hours and 3 days, the origin of which is unknown. The pain is usually throbbing and affects only one side of the head, but sometimes it can be bilateral. The pain is usually moderate to severe and is aggravated by head movement, making it difficult to perform daily activities. In addition to the headache, migraine without aura is associated with other symptoms such as nausea, vomiting, sensitivity to light and sound, and sometimes to certain odors. The diagnosis is made based on criteria established by the "International Headache Society".

What is migraine with aura?

Migraine with aura is a disorder that usually includes reversible visual symptoms, such as spots or flashes, which may be accompanied by unilateral sensory symptoms. In less common cases, temporary speech problems may be experienced. These symptoms usually develop in about five minutes and do not last more than an hour. Although they can be self-limiting without further symptoms, they are commonly accompanied by migraine-like headaches within a period of no more than 60 minutes.

Bibliographic references

• Maintz et al. Histamine and histamine intolerance. Am J Clin Nutr 2007; 85:1185-1196.

• Jarisch et al. Histamin-intolerance. Histamin and Seekrankheit, 2 edn. Stuttgart, Germany: Georg Thieme Verlag KG, 2004.
• Izquierdo-Casas et al. Low serum diamine oxidase (DAO) activity levels in patients with migraine. J Physiol Biochem 2018;74(1):93-99.
• Garcia-Martin et al. Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk for migraine. Headache 2015;55(2):276-86.
• A. Duelo et al. Low-histamine diet supplemented with exogenous diamine oxidase enzyme is useful for treating migraine in patients with DAO Deficiency. Ann Nutr Metab 2018;73 (suppl 2); 1-93
• Izquierdo-Casas et al. Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial. Clin Nutr. 2018 Feb 15. pii: S0261-5614(18)30014-1
• Maintz et al. Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities. Allergies 2001; 66:893-902.
• Steinbrecher and Jarisch 2005, Histamine and headache. Allergologie 28: 85-91