Fibromyalgia, chronic fatigue and muscle pain produced by DAO deficiency

The main characterising element of fibromyalgia is the  diffuse and widespread musculoskeletal pain or stiffness prominent that affects at least 3 anatomical locations for more than 3 months

Defined by Fibromyalgia (FM) (etymologically the term derives from the latin and greek: muscle pain of connective tissue) a group of symptoms and musculoskeletal disorders which are characterized all by the extreme fatigue, persistent pain, stiffness of variable intensity of muscles, tendons and surrounding soft tissue, and a wide range of other psychological symptoms, such as difficulty sleeping, morning stiffness, headaches and memory problems (the so-called “mental” lagoons – that often impede the routine functioning of the subject.

Their diagnosis has been controversial due to the lack of abnormalities on physical examination, laboratory tests and objectives or in medical imaging studies to confirm the diagnosis. Today there are new biomarkers, such as the activity of the enzyme diamine oxidase (DAO), for those that have been developed diagnostic methods and new treatments.

Symptoms of fibromyalgia, chronic fatigue and generalized muscle pain

The main characterising element of fibromyalgia is the  diffuse and widespread musculoskeletal pain or stiffness prominent that affects at least 3 anatomical locations for more than 3 months, without which you cannot perform the diagnosis of the disorder. The pain is usually severe and in many cases difficult to describe, and, in general, is worse with intense physical exercise, cold and emotional stress.

Frequent sites where symptoms of fibromyalgia appear include the lumbar region, neck, trapezes, chest and thighs. In some cases, muscle spasm and/or contractures located.

Additional symptoms may include headache, migraine, restless legs syndrome, difficulty concentrating and difficulty remembering things, tinnitus and some neurological symptoms of motor incoordination.

Between 70 and 90% of those suffering from fibromyalgia refer also sleep disorders, expressed as a unrefreshing sleep, light and unstable. Typically associated in addition intense weakening (asthenia), alterations of the intestinal rate, stiffness in the upper or lower limbs, and very often major depressive episodes accompanied by anxiety crisis.

Fatigue in extreme degree is present in all the activities carried out by people with fibromyalgia, so their daily tasks are inevitably hampered. Depending on the severity and the variation in the degree, this fatigue can be from bearable until a disability almost impassable barrier that limits their tasks both within the family and professional capacity.

Related to fatigue, as cause that increases and aggravates, is the poor quality of sleep, which prevents those who have this condition have a restful sleep and, therefore, will prevent the rest what it will accentuate the tiredness and fatigue in the future.

Role of histamine in the etiology of fibromyalgia, chronic fatigue and generalized muscle pain

With regard to treatment, it is considered that currently there is no cure for fibromyalgia and treatments are aimed at the alleviation of symptoms, being necessary the intervention of a multidisciplinary team. Between the treatments used until the knowledge of its relationship with the deficiency of the enzyme activity diamine oxidase (DAO), were the antidepressants, muscle relaxants, inhibitors of serotonin, NSAIDS. In addition, have been considered suitable rehabilitation, aliviomiofacial cranosacral therapy, massage, chiropractic, osteopathy, stretching exercises and/ aerobics, the training of posture, occupational therapy, relaxation, conduct and acupuncture.

Musculoskeletal pain, common to all people who suffer from fibromyalgia and chronic fatigue syndrome, as well as other additional symptoms of both diseases are the result of the dilation of blood vessels by the effect of some vasodilators substances, mainly the histamine in the body, as well as by the accumulation and deposit of histamine in muscle tissue. In this way the histamine has a direct effect on the different manifestations of pain, common to people who suffer from fibromyalgia and chronic fatigue, playing a key role in these processes of pain.

The histamine [2-(4-imidazolil)-ethylamine] is an important mediator of many biological processes including inflammation, the secretion of gastric acid, neuromodulation and regulation of immune function. Histamine is produced by human beings themselves and is stored in an inactive form in the methacromatic granules of mast cells and basophils leukocytes where it is available for immediate release. After the liberation, histamine is an extraordinarily powerful mediator of a plurality of physiological and pathophysiological processes, often also through interaction with cytokines.

Histamine can also enter the human body from the outside, as it is generated by microbial action in the course of the food processing and, therefore, it is present in substancial quantities in many foods and fermented beverages.

Therefore after the intake of certain foods there is a substantial increase of histamine in circulation.

Enzyme diamine oxidase (DAO): A New Biomarker for fibromyalgia, chronic fatigue and generalized muscle pain

The main route of inactivation of histamine swallowed is the  oxidative deamination of primary amino group, catalyzed the enzyme diamine oxidase (DAO) to give imidazolacetaldehide.

The main function of the DAO is to prevent the histamine ingested by the power reaches the blood circulation from the intestine. In addition to the histamine, DAO can degrade other biogenic amines, such as putrescine, spermidine and cadaverine. It has a molecular weight of approximately 182 kDa and a proportion of carbohydrates of 11%. Belongs to the class of the amine-oxidases containing copper and that catalyze the oxidative deamination of primary amines to give aldehydes, ammonia and hydrogen peroxide. The DAO uses molecular oxygen for deaminate histamine to imidazolacetaldehide by oxidation, ammonia and hydrogen peroxide.

The DAO is found mainly in the small intestine, liver, kidneys and in leukocytes from the blood. Pregnant women are at a level of DAO in blood of approximately 500 to 1000 times higher than non-pregnant women, because they produce DAO additionally in the placenta to protect the fetus during its development (therefore, during pregnancy tend to disappear the fibromyalgia symptoms). Histamine is produced continuously in the human being and is excreted by intestinal tract, being degraded by passing through the intestinal mucosa by the DAO that is there.

DAO is a sensitive enzyme that can be inhibited by various substances, such as other biogenic amines, by alcohol and by its breakdown product acetaldehyde, as well as for different medications, paradoxically prescribed for palliative treatment of muscle pain and fibromyalgia.

In addition to the inhibition of the DAO by certain types of substances, there is a significant percentage of the population whose levels of DAO in blood are abnormally low, which implies that the level of histamine in the blood is higher than the values considered normal (2-20 micrograms/0.1 L). In this type of subjects are triggered a whole series of pathologies caused by these high levels of histamine in the blood, including fibromyalgia and/or muscle pain.

Diagnosis and treatment of fibromyalgia, chronic fatigue and generalized muscle pain caused by DAO deficiency: DAO Treatment and DAO activity

The determination of DAO, therefore, represents a new and important biomarker for the objective diagnosis of Fibromyalgia and Chronic Fatigue, both by a genetic study of implied genotypes and a plasmatic measure of its activity or a combination of both.

After a diagnosis of fibromyalgia, chronic fatigue syndrome or generalized muscle pain and deficit of DAO, proactive management and treatment with DAO supplementation has the effect of contributing to the degradation of excess histamine, thus preventing the development of symptoms.

The DAO treatment consists in the supplementation of the diet with exogenous DAO along with a poor diet in foods with high content of histamine and/or liberators, thereby also contributing the administration of an adjuvant, such as magnesium. In the design of the DAO treatment should also be taken into account to avoid as far as possible the use of drugs identified as liberators of histamine and/or inhibitors of DAO.

In this way, the DAO treatment represents a new approach in preventive therapy for fibromyalgia, chronic fatigue and generalized muscle pain with minimal risk of adverse effects as a dietetic food.

Access to the scientific and clinical evidence of fibromyalgia, chronic fatigue and generalized muscle pain by DAO deficiency

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