The use of oral magnesium preparations for the treatment of cardiovascular diseases

Over 80,000 clinical, biochemical, and cellular molecular studies published over the past 30 years indicate that adequate levels of magnesium in the body are a fundamental indicator of human health.

However, modern lifestyle, which usually includes high levels of stress, an unbalanced diet with the presence of large amounts of artificial foods, inevitably leads to magnesium deficiency.

In this article I will tell you how and why magnesium is needed, which dietary supplements with magnesium to choose and how to take it correctly.

Important facts:
1. The intracellular concentration of magnesium in the body decreases with age1.
2. Magnesium increases the effectiveness of glucose-lowering therapy in patients with type 2 diabetes mellitus2.
3. Magnesium is not produced by the body and can only be obtained from food or supplements3.
4. Magnesium reduces the risk of developing Alzheimer's disease and improves memory. This is due to the fact that this mineral reduces the risk of developing amyloid plaques in the hippocampus and prefrontal cortex, and enhances the work of synaptic nerve endings responsible for the transmission and storage of information (short-term and long-term memory).
5. The three leading factors contributing to the excretion of magnesium are: stress, alcohol, tobacco.

IMPORTANT!

If you have excess calcium and not enough magnesium, this can lead to the development of tissue calcification. After all, it is magnesium that converts vitamin D into its active form! Therefore, please note: if you are recommended to take large doses of vitamin D, which helps calcium to be absorbed well, taking magnesium is a must!

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Symptoms that may indicate low magnesium levels:

• headaches, dizziness;
• constant fatigue, apathy;
• sleep disorder;
• poor quality of nails and hair;
• anxiety, depression;
• indigestion (nausea, heartburn, constipation);
• cramps and spasms in the lower extremities.

In children, deficits may manifest themselves in:

• low concentration;
• increased excitability;
• decreased memory;
• increased irritability;
• hyperactivity.

Magnesium deficiency is dangerous due to the development of:

• urolithiasis and cholelithiasis;
• increased blood cholesterol;
• development of cardiovascular diseases;
• carbohydrate metabolism disorders;
• development of insomnia.

SportExpert Liquid magnesium, 8 doses of 50 ml, Evalar

415 ₽

Dietary supplement NOT A MEDICINE

Magnesium and sports

Some more important and interesting facts about magnesium:

1. In marathon runners, after a 42 km race, a significant decrease in the concentration of magnesium in the blood serum was recorded against the background of an increase in potassium and sodium levels5.
2. In middle- and long-distance runners, an ergometer test showed a significant increase in serum calcium and magnesium levels, however, against the background of an increase in cortisol and thyroid hormone levels, the level of magnesium in red blood cells significantly decreased6. However, magnesium supplementation improves blood glucose metabolism, reduces the inflammatory response, and reduces muscle soreness after exercise7.
3. When swimming, plasma magnesium levels decrease even in experienced swimmers. This is due to the participation of this mineral in thermoregulation, and we know that swimming is a sport that requires constant maintenance of body temperature in water8.

It is important to remember that hormone levels, particularly adrenaline and insulin, change significantly during exercise and require additional magnesium supplementation, since magnesium ions are necessary to maintain normal receptor sensitivity to these hormones.

Chronic magnesium deficiency contributes to impaired fat metabolism, changes in blood sugar levels9, and increased blood pressure during physical activity10.

Reduced levels of magnesium in the blood, associated with insufficient intake, against the background of physical exercise stimulate the development of inflammatory processes and contribute to the development of immunological disorders11.

Magnesium preparations in cardiological practice

Despite the achievements of modern medicine, cardiovascular diseases (CVD) in the Russian Federation, as well as throughout the world, remain one of the most common diseases that practitioners have to deal with. First of all, this is, of course, arterial hypertension (AH), coronary heart disease (CHD) and chronic heart failure (CHF). These diseases are the main cause of death in both developed and developing countries [1]. This makes the problem of optimizing pharmacotherapy in order to reduce cardiovascular risk extremely important, and the search for an individual approach to the management of patients with various CVDs and a differentiated choice of drugs remains an urgent problem for the practicing physician. Today, a doctor has a wide selection of effective pharmacological agents for the treatment of various CVDs, which should be prescribed following the relevant Russian and international recommendations based on a large evidence base.

In recent years, the use of drugs that affect the balance of micro- and macroelements (sodium, potassium, calcium, magnesium, chlorine, phosphorus, sulfur, etc.), which are necessary for the normal functioning and performance of the body and which the human body is not able to synthesize on its own, has become promising. . Maintaining a normal level of these elements is only possible if an adequate amount of them is supplied with food. An optimally balanced diet helps maintain normal levels of macro- and microelements. But these are only ideal conditions, rarely achievable in modern life.

One of the most common types of mineral deficiency in many countries is magnesium deficiency, which occupies one of the leading places in human pathologies caused by disorders of mineral metabolism (manganese, iodine, zinc, copper, calcium), and, according to the International Classification of Diseases, 10th revision , is registered as a separate disease - E 61.2 [2, 3].

Data from a number of observations indicate that from 25% to 40% of the adult population are deficient in this important macronutrient.

Given the prevalence of magnesium deficiency, it is expected that a large number of patients with cardiovascular disease will have magnesium deficiency of varying severity.

Mechanism of action of magnesium

One of the macroelements important for the body is magnesium. From the point of view of biological function, magnesium is a cofactor and activator of a number of enzymes - enolase, alkaline phosphatase, carboxylase, hexokinase. Another role of magnesium ions is stabilizing. Magnesium ions stabilize the substrate molecules - they neutralize the negative charge of the substrate, the active center of the enzyme, help maintain the tertiary and quaternary structures of the enzyme protein molecule, facilitate the attachment of the substrate to the enzyme and thereby facilitate the chemical reaction, the magnesium-ATP complex, stabilizing the ATP molecule, facilitating its attachment and “correct” orientation in the active site of the enzyme, weakening the phosphoester bond and facilitating the transfer of phosphate to glucose. In some cases, magnesium ion can help attach the coenzyme, promoting the activation of metalloenzymes.

Magnesium contributes to the stability of the cell structure during growth and takes part in the process of regeneration of body cells.

Data have been obtained confirming the irreplaceable role of magnesium in the absorption of vitamins B1 (thiamine), B6 ​​(pyridoxine) and vitamin C [4, 5].

The participation of magnesium in phosphorus and carbohydrate metabolism, in protein synthesis, and in the transmission of neuromuscular impulses has been established [4].

Magnesium is involved in maintaining the electrical potential of membranes, promotes the penetration of calcium, sodium, and potassium ions through them, and takes part in the transmission of nerve impulses. It regulates the passage of the inhibition signal from the central parts of the nervous system to the peripheral nervous system. With a lack of magnesium, the nervous system remains in a state of overexcitation and, as a result, chronic stress is observed. Magnesium, in turn, is called an anti-stress element.

Magnesium can affect calcium levels by influencing hormones that control calcium absorption and metabolism. In the regulation of vascular tone, magnesium and calcium ions act as antagonists: calcium plays a leading role in the contraction of smooth muscles of blood vessels, magnesium, on the contrary, in their expansion, promotes the elimination of excess cholesterol, the absorption of calcium and phosphorus.

Magnesium is able to increase insulin secretion and improve its penetration into cells. It is also necessary for the production of brain neuropeptides, stimulates intestinal motility, promotes the secretion of bile, and is involved in the production of catecholamines.

Lack of magnesium in the body

Since magnesium ranks 4th in content in the body, it is natural that with chronic magnesium deficiency, functional disorders occur in many organs and tissues.

Magnesium deficiency can be caused by changes in its distribution between blood serum and cells, decreased dietary intake, or excessive loss. Unlike primary magnesium deficiency, which is associated with a person’s constitutional characteristics, secondary magnesium deficiency is associated with living conditions or diseases.

Living conditions that cause magnesium deficiency:

• insufficient food intake (nutritional deficiency), intravenous therapeutic nutrition;
• hypocaloric diet, unbalanced diet (excessive levels of lipids, calcium, phosphates);
• stress, strenuous physical work;
• physical inactivity;
• exposure to high temperatures;
• increased consumption of magnesium during pregnancy, intensive growth, recovery, with excessive sweating, with excessive physical exertion, with chronic alcoholism;
• hormonal contraception.

Magnesium deficiency associated with diseases and their therapy:

• impaired absorption of macronutrients in the intestine (disease of the small intestine, reduction in the absorptive surface of the intestine after surgery or during radiotherapy, steatorrhea, dysbiosis in the large intestine); impaired insulin production;
• nephrotic syndrome;
• hypercortisolism;
• hypercatecholaminemia;
• hyperaldosteronism;
• hyperthyroidism;
• arterial hypertension;
• myocardial infarction;
• obesity;
• diuretic, cytostatic therapy;
• long-term use of antibiotics (gentamicin), diuretics, antitumor and other medications;
• poisoning with certain substances (aluminum, lead, cobalt, manganese, cadmium, beryllium, nickel).

Physiological effects of magnesium

Due to the combination of such properties inherent in this element, the physiological effects of magnesium are very diverse and are manifested in the fact that it has a beneficial effect on bone growth; helps slow heart rate, reduces high blood pressure; promotes bronchodilation; used as a prophylactic for muscle and joint pain, chronic fatigue syndrome, migraines, etc.

The effects of magnesium on the cardiovascular system are extremely important:

• hypotensive effect - has a hypotensive effect due to negative chrono- and inotropic effects, decreased vascular tone, inhibition of transmission in the autonomic ganglia, inhibition of the vasomotor center;
• anti-ischemic effect - due to the restoration of endothelium-dependent vasodilation, normalization of lipid spectrum indicators, improvement of rheological properties of blood, reduction of platelet aggregation activity, depressor effect on the inotropic function of the heart [6–8];
• antiarrhythmic effect - magnesium has a membrane-stabilizing effect, a depressor effect on the excitability and conductivity of the cell [9]. Depletion of magnesium stores causes significant adverse effects on the myocardium [10]. Violation of the content of potassium and magnesium ions and their ratio is a significant risk factor for the development of arrhythmias. In the Framingham Study, extrasystoles were detected in 5.5% of study participants (n = 3327, mean age 44 years). At the same time, long-term hypomagnesemia correlates with a high incidence of ventricular extrasystoles, tachycardia, and ventricular fibrillation (p = 0.01). This pattern remained significant even after taking into account adjustments for left ventricular mass, including in volunteers without clinically significant disease [11]. The PROMISE Study revealed a higher incidence of ventricular extrasystole and high mortality in the group of patients with hypomagnesemia compared to groups with normo- and hypermagnesemia [12];
• effect on connective tissue - magnesium affects collagen metabolism, reducing the severity of dysplastic changes in connective tissue [13, 14].

In recent years, among the possible pathogenetic mechanisms for the formation of mitral valve prolapse, some researchers point to a chronic deficiency of magnesium ions, which leads to disruption of the formation of connective tissue structures of the supporting trophic framework of the heart, which causes a chaotic arrangement of collagen fibers, disruption of its synthesis and biodegradation [15].

Magnesium ions are of great importance for the normal functioning of connective tissue. In a number of animal experiments, it was shown that magnesium deficiency leads to an increase in the activity of collagenases, in particular matrix metalloproteinases, while the metabolism of the structural components of the extracellular matrix, primarily collagen, was disrupted. Along with an increase in the activity of metalloproteinases, magnesium deficiency reduces the enzymatic activity of transglutaminases and lysyl oxidases involved in the formation of cross-links, resulting in a decrease in the mechanical strength of collagen fibers [15–17].

Symptoms of magnesium deficiency

Signs of magnesium deficiency are nonspecific. Clinically, magnesium deficiency can manifest itself in the form of endocrine-metabolic, mental and neurological disorders, in the form of disorders of various organs and systems, including the cardiovascular and musculoskeletal system.

The main complaints presented by patients: paresthesia in the form of impaired sensitivity, sensations of numbness, tingling, itching, crawling, etc., muscle cramps, increased neuromuscular excitability, fatigue, sudden dizziness accompanied by loss of balance, irritability, insomnia , nightmares, difficult awakening, deterioration in concentration, loss of appetite, constipation, nausea, diarrhea, vomiting, increased blood pressure, arrhythmias, angina pectoris, vasospasms, atrophic skin manifestations in the form of hair loss, increased brittleness of nails.

Examinations may reveal signs of dysfunction of the adrenal glands, the development of diabetes mellitus, urolithiasis and cholelithiasis, and immunodeficiency states. Such patients have an increased likelihood of developing tumor diseases.

Since the metabolism of magnesium and calcium is closely related, with magnesium deficiency the calcium level also decreases and osteoporosis develops. This is also facilitated by dysfunction of the parathyroid gland.

The cardiovascular system also responds to magnesium deficiency: patients experience accelerated progression of atherosclerosis, tachycardia, arrhythmias, mitral valve prolapse, and a decrease in the electrical stability of the myocardium, characterized by an increase in the dispersion and/or duration of the QT interval. In such patients, an increase in mortality from coronary artery disease was observed.

There is an opinion that cases of early myocardial infarction among people aged 30–40 years are associated with reduced magnesium content in the heart muscle.

Clinical experience with the use of magnesium preparations in cardiology

It is obvious that magnesium deficiency in diseases of the cardiovascular system cannot be compensated only by changing the diet; the use of magnesium preparations is necessary.

Inorganic magnesium preparations, such as magnesium sulfate, have extremely low bioavailability of magnesium and have a number of pronounced side effects [4, 18].

To compensate for magnesium deficiency, it is necessary to use magnesium preparations characterized by high bioavailability - organic magnesium preparations [19].

One of these drugs is Magnerot - a salt of magnesium and orotic acid. Orotic acid is one of the products of pyrimidine biosynthesis. In the human body, orotic acid is synthesized in the liver from aspartate and carbamoyl phosphate, subject to the physiological state of hepatocytes. Orotic acid salts are used as a mineral carrier, since orotic acid increases targeted transport into skeletal muscle myocytes and cardiomyocytes, and also has a number of additional advantages compared to inorganic salts.

To date, a large evidence base has been accumulated indicating the high effectiveness of magnesium orotate in various conditions accompanied by magnesium deficiency, including in patients undergoing coronary surgery [3, 7, 20–24].

The greatest experience in the use of magnesium orotate is in patients with mitral valve prolapse (MVP) as pathogenetic therapy. A long-term, over 15 years, observation of patients who took the drug at a dose of 1500 mg/day twice a year for 3 months showed that this leads to an improvement in clinical condition and is accompanied by a decrease in heart rate, number of episodes of tachycardia, duration QTc interval, frequency of paroxysmal supraventricular tachycardia, supraventricular and ventricular extrasystole [25]. The use of magnesium orotate in patients with mitral valve prolapse also improves quality of life and echocardiography indicators (reducing the depth of mitral valve prolapse, reducing the degree of mitral regurgitation) [26]. These effects are realized due to the fact that the drug causes changes in the architectonics of loose fibrous connective tissue, manifested in the orderliness of the relative arrangement of fibers, an increase in the content of amorphous substance of loose fibrous connective tissue involved in the metabolic processes of the myocardium, improved diffusion capacity and architectonics of connective tissue, which determines improved elasticity and extensibility [27].

The anti-ischemic effect of magnesium is manifested due to a positive effect on endothelium-dependent vasodilation [6], as well as normalization of metabolism in ischemic tissues, and a depressor effect on the inotropic function of the heart [8]. These same effects also explain the positive dynamics in patients with severe CHF when magnesium is included in complex therapy [7].

The drug is also effective in the prevention of supraventricular tachyarrhythmias during surgical interventions in patients with combined cardiac and urological pathologies. If the drug is prescribed before surgery, the likelihood of arrhythmia decreases by 16% [9].

An important positive aspect of magnesium preparations in cardiological practice is also that they can be used for the correction and prevention of hyperkalemia associated with long-term courses of potassium-sparing diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, as well as associated with the presence of metabolic syndrome. With the use of magnesium orotate, the well-being of patients improves and laboratory parameters are normalized [28].

Thus, magnesium deficiency is one of the most common types of mineral deficiency, occurring in 25–40% of the adult population. Literature data and more than 20 years of experience in the clinical use of magnesium preparations indicate their good effectiveness and high safety profile in patients with various cardiac pathologies.

Literature

1. Ezzati M., Lopez A., Rodgers A., Vander Hoorn S., Murray CJL eds. Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors. Geneva: World Health Organization; 2004.
2. Bourre JM Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients // J. Nutr. Health Aging. 2006; 10 (5): 377–385.
3. Classen HG Magnesium orotate-experimental and clinical evidence // Rom. J. Intern. Med. 2004; 42(3):491–501.
4. Gromova O. A. Magnesium and pyridoxine. Basic knowledge. M.: ProtoTip, 2006. 234 p.
5. Torshin I. Yu., Gromova O. A., Gusev E. I. Mechanisms of anti-stress and antidepressant action of magnesium and pyridoxine // Journal of Neurology and Psychiatry. 2009, No. 11, p. 107–111.
6. Kirichenko A. A., Flegentova O. N., Novichkova Yu. N., Vinogradova I. V., Ryazantsev A. A., Yurchenko K. V. Effect of therapy with Magnerot on cardialgia in postmenopausal women // Attending Physician. 2005. No. 5. P. 76 –77.
7. Stepura OB, Martynow AI Magnesium orotat in severe congestive heart failure (MACH) // Int J Cardiol. 2009, May 1; 134(1):145–147.
8. Ezhov A.V., Pimenov L.T., Zamostyanov M.V. Clinical effectiveness of Magnerot in the treatment of stable angina pectoris in combination with arterial hypertension in the elderly // Ros. honey. lead. 2001. No. 1. P. 71–74.
9. Davydova S., Yarovoy S. Magnesium preparations in the treatment and prevention of supraventricular tachyarrhythmias in urological patients // Doctor. 2011. No. 9. pp. 44–49.
10. Chakraborti S., Chakraborti T., Mandal M. et al. Protective role of magnesium in the cardiovascular diseases: A review // Mol Cell Biochem. 2002; 238:163–179.
11. Tsuji H., Venditti FJ Jr., Evans JC et al. The associations of levels of serum potassium and magnesium with ventricular premature complexes (the Framingham Heart Study) // Am J Cardiol. 1994; 74:232–235.
12. Eichhorn EJ, Tandon PK, Dibianco R. et al. The Study Group Clinical and prognostic significance of serum magnesium concentration in patients with severe chronic congestive heart failure: The Promise Study // J Am Coll Cardiol. 1993; 21(3):634–640.
13. Libova L. T., Dobrynina V. A., Kalenik S. A., Brovkina E. G. Use of the drug MAGNEROT® for mitral valve prolapse and stage I hypertension // New Millennium Medicine. 2011. No. 4. P. 3–4.
14. Martynov A.I., Akatova E.V., Nikolin O.P. Clinical effectiveness of magnesium orotate in patients with rhythm disturbances and arterial hypertension with mitral valve prolapse // Cardiovasc. therapy and prevention. 2009; 8:8–12.
15. Baker P., Bansal G., Boudoulas H. et al. Floppy mitral valve chordae tendineae: histopathologic alterations // Hum Pathology. 1998; 19(5):507–512.
16. Kitlinski M., Konduracka E., Piwowarska. Evaluation of magnesium cation levels in serum of patients with mitrale valve prolapse syndrome // Folia Med Cracov. 2000; 41 (3–4): 17–24.
17. Disse S., Abergei E., Derrebi A. et al. Mapping of the first locus for autosomal dominant myxomatous mitral valve prolapse to chromosome 16 p11.2–p.12.1 // Am J Hum Genet. 1999; 65(5):1242–1251.
18. Lazebnik L. B., Drozdova S. L. Correction of magnesium deficiency in cardiovascular pathology // Cardiology. 1997; 5: 103–104.
19. Tokimasa T., Akasu T. Cyclic AMP regulates an inward rectifying sodiumpotassium current in dissociated bull-frog sympathetic neurons // J Physiol. 1990; 420:409–429.
20. Jellinek H., Takacs E. Morphological aspects of the effects of orotic acid and magnesium orotate on hypercholesterolaemia in rabbits // Arzneimittelforschung. 1995. Vol. 45. No. 8. P. 836–884.
21. Geiss KR, Stergiou N., Neuenfeld HU, Jester HG Effects of magnesium orotate on exercise tolerance in patients with coronary heart disease // Cardiovasc Drugs Ther. 1998; 12: 153–156.
22. Ezhov AV, Pimenov LT Effect of adjuvant magnesium therapy on the quality of life and emotional status of elderly patients with stable angina // Adv Gerontol. 2002; 10: 95–98.
23. Salerno C., Crifo C. Diagnostic value of urinary orotic acid levels: applicable separation methods // J Chromatogr B Analyt Technol Biomed Life Sci. 2002; 781:57–71.
24. Motyl T., Krzeminski J., Podgurniak M. et al. Variability of orotic acid concentration in cow's milk // Endocr Regul. 1991; 25: 79–82.
25. Akatova E.V., Martynov A.I., Nikolin O.P. Results of long-term therapy with magnesium orotate in patients with mitral valve prolapse // Cardiovascular Therapy and Prevention. 2012; 3:30–35.
26. Akatova E.V., Martynov A.I. 15-year experience of using magnesium in patients with MVP // Cardiology. 2011.
27. Avtandilov A. G., Dzeranova K. M., Borovaya T. G., Didenko L. V. Effect of magnesium orotate on the connective tissue framework and inotropic function of the heart in patients with mitral valve prolapse. Clinical and morphological study // Rational pharmacotherapy in cardiology. 2013; 9 (4): 390–397.
28. Limanova O. A., Fedotova L. E., Kalacheva A. G., Torshin I. Yu., Gromova O. A. Management of patients with hyperpotassium conditions (cases from practice) // Zemsky Vrach. 2013; 4 (21), 24–32.

T. E. Morozova1, Doctor of Medical Sciences, Professor O. S. Durnetsova

GBOU VPO First Moscow State Medical University named after. I. M. Sechenova Ministry of Health of the Russian Federation, Moscow

1 Contact information

Magnesium Citrate, 60 Tablets, Solgar

Magnesium citrate (magnesium salt of citric acid) has been used in therapy for more than 50 years and is used to prevent the formation of kidney stones, prevent and treat hypomagnesemia.

Magnesium salt of citric acid has a high safety profile and is acceptable for use in case of kidney problems. Unlike inorganic salts, this form leads to better absorption of magnesium with reduced stomach acidity compared to magnesium lactate and other organic forms of magnesium.

Magnesium chelate, 60 tablets, Evalar

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Dietary supplement NOT A MEDICINE

Types of seizures

All categories of people can experience seizures, regardless of age and lifestyle; they appear more often in the elderly and young children. Attacks are manifested by unequal painful muscle contractions and have different durations, mechanisms of development and frequency of occurrence. They are classified according to several criteria.

By locality

Depending on whether one muscle or a group of them is seized by a spasm, spasms are divided into:

• unilateral – when pain occurs on one side;
• focal (local) - appear in one muscle group;
• generalized - affect the whole body, causing involuntary urination, loss of consciousness and even respiratory arrest.

By duration of exposure

Classified into:

• myoclonic - short-term contractions or twitches, mainly in the upper part of the body, stop quickly and do not cause pain;
• clonic - characterized by a longer duration, muscles contract rhythmically, can be of a local or general type, sometimes contribute to stuttering;
• tonic – long-term, can occur in any part of the body, affect the respiratory tract, the part of the body seized by a convulsion takes one forced position, can lead to loss of consciousness;
• tonic-clonic - in which tonic spasms turn into clonic; if the second type predominates, they are called clono-tonic.

Magnesium B6 solution, 100 ml, Evalar

Pay attention to the liquid form of Magnesium from the Evalar company, which can be given to both children from three years old and pregnant/lactating women, because it contains metal ions, a natural thickener, purified water and citric acid as a stabilizer. It has a high safety profile, and due to its liquid form it is effective. This form is also suitable for vegetarians.

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How to prevent seizures

Measures aimed at eliminating and preventing the occurrence of seizures should include:

- giving up harmful addictions (smoking, excessive consumption of alcohol, coffee, tonic drinks); — sufficient daily fluid intake; — physical education to improve blood circulation; - enriching the body with vitamins and microelements (deficiencies in specific compounds can be identified using tests); - Night cramps can be prevented by a warm bath or shower.

To treat and prevent seizures, purchase a complex containing magnesium as a therapeutic measure. Even if there is no deficiency of this mineral in the body, it acts as an anticonvulsant element that reduces neuromuscular excitability.