Nature Made High Potency Magnesium 400 mg Softgels, 110 count
The role of magnesium in diseases of the cardiovascular system
The word "magnesium" comes from the name of the Greek city of Magnesia, next to which large deposits of magnesium carbonate were found. Among all the cations, magnesium takes the 4th place by the content in the human body after K +, Na +, Ca2 + and the 2nd place after K + by the content in the cell. Up to 53% of magnesium is concentrated in bone tissue, dentin and tooth enamel, and about 20% in tissues with the highest metabolic activity (brain, heart, muscles, kidneys, liver).
In humans, the amount of magnesium is about 20-28 grams - mostly within the cells themselves, where, along with potassium, it is the second most important mineral substance. Only 1% of magnesium is in the blood. It is a macronutrient, natural calcium antagonist and a regulator of vascular tone, blood pressure and peripheral circulation.
Magnesium activates ATPase, an essential enzyme for the functioning of the cell membrane and an energy source for the Na – K pump. Intracellular magnesium deficiency can cause an increase in the content of sodium and calcium in the cell and a decrease in the potassium content [1]. Despite the important role of magnesium, its level is determined quite rarely, although in one study, hypomagnesemia was detected in 42% of hospitalized patients, hypermagnemia in 6% [2].
At the same time, the level of magnesium, like potassium, in the blood serum often remains normal, despite the decrease in its content in the body. In general, neither the serum level, nor the determination of the intracellular magnesium content gives a correct idea of its physiological activity, in contrast to the determination of free magnesium, which is possible by magnetic resonance imaging [3]. However, in clinical practice, only determination of the serum level of magnesium is available. Despite the fact that almost all magnesium is in the body intracellularly, a low level of its content in serum correlates with a general deficiency of magnesium [4].
Epidemiological studies have shown that serum magnesium levels are inversely associated with risk factors for cardiovascular diseases, such as hypertension, type 2 diabetes, metabolic syndrome, and ischemic heart disease [5].
Other data obtained during environmental, clinical studies, autopsies, suggest that increasing the level of magnesium potentially protects against cardiovascular disease [6].
The physiological role of magnesium
in the body
Magnesium affects the regulation of biochemical processes in the body through magnesium-containing enzymes and free magnesium ions (being a cofactor of many enzymatic reactions (hydrolysis and transfer of the phosphate group, the functioning of Na + –K + –ATP pump, Ca2 + –ATP pump, proton pump, participates in the exchange of electrolytes, hydrolysis ATP, reduces the separation of oxidation and phosphorylation, regulates glycolysis and fatty acid oxidation; participates in protein biosynthesis, transfer of genetic information, synthesis of cyclic AMP and synthesis of nitric oxide in ndothelium of blood vessels).
In addition, magnesium is involved in maintaining the electrical equilibrium of the cell (including in the process of depolarization, with a lack of magnesium, the cell becomes super-excitable).
Magnesium has an inhibitory effect on the conduction of nerve impulses, is part of numerous enzymes of the nervous and glial tissues, participates in the processes of synthesis and degradation of neurotransmitters (norepinephrine, acetylcholine), as well as in the regulation of the neuromuscular activity of the body's conducting tissues smooth muscles of internal organs), because it prevents the entry of calcium ions through the presynaptic membrane, which determines the presence of myotropic, antispasmodic and disaggre NAVIGATION effects.
This element is a component of the antioxidant system, an important component of the immune system. It inhibits the premature involution of the thymus, regulates the phagocytic activity of macrophages, the interaction of T– and B – lymphocytes.
Being next to calcium in the group of the periodic system, magnesium is a calcium antagonist: these two elements easily displace each other from the compounds. Magnesium deficiency in a diet rich in calcium causes calcium retention in all tissues, which leads to their calcification [7].
Magnesium enters the body with food (in particular with table salt) and water. The rate of intake is usually 200-400 mg during the day. The plant food is especially rich in magnesium: legumes and cereals, spinach, salads, nuts. However, the magnesium content in them can vary significantly depending on the soil of growth. Water is also an important source, and the harder it is, the higher its magnesium content. In regions with soft water, the frequency of occurrence of hypomagnesia is high. Part of ionized magnesium is cleaved from the magnesia salts of food even in the stomach and absorbed into the blood. The bulk of the sparingly soluble magnesium salts passes into the intestines and is absorbed only after they are combined with fatty acids. In the gastrointestinal tract absorbs up to 40-45% of incoming magnesium. In human blood, about 50% of magnesium is bound, and the rest is ionized. The concentration of magnesium in the blood of a person is 2.3-4.0 mg. Complex compounds of magnesium enter the liver, where they are used for the synthesis of biologically active compounds. The main "depot" of magnesium is in the bones and muscles. Magnesium is eliminated from the body mainly with urine (50–120 mg) and with sweat (5–15 mg). The absorption of magnesium increases with its deficiency in the body. For digestion, the body requires a sufficient amount of cofactors: lactic, aspartic, orotic acids, and vitamin B6. Vitamins B1, B6, C, D, E, calcium, phosphorus (supplied in optimal amounts), protein, estrogen increase the level of magnesium in the body [7]. Magnesium is excreted mainly by the kidneys, also with sweating.
Causes of magnesium deficiency can be:
• insufficient supply (regions with “soft” water ”);
• impaired intestinal absorption (dysbacteriosis, chronic duodenitis);
• violations of the regulation of magnesium metabolism;
• decrease in digestion under the action of excess phosphates, calcium and lipids;
• long-term use of antibiotics (gentamicin), diuretic, antitumor and other pharmacological drugs;
• parenteral nutrition;
• increased need for magnesium (during pregnancy, during growth and recovery, in chronic alcoholism, excessive sweating);
• violation of insulin synthesis;
• intoxication with aluminum, beryllium, lead, nickel, cadmium, cobalt and manganese.
Magnesium deficiency is the most common type of mineral deficiency among the population in many countries, particularly in the United States.
The main manifestations of magnesium deficiency:
• fatigue, irritability;
• insomnia disorders, dizziness;
• loss of appetite, nausea, vomiting, diarrhea, constipation;
• cardialgia, palpitations, fluctuations in blood pressure (BP), prolongation of the QT interval;
• arrhythmias, angiospasms, muscle weakness, muscle cramps;
• immunodeficiency (possibly increased risk of neoplastic diseases);
• bronchospasm and laryngism;
• paresthesias, smooth muscle spasms.
Magnesium deficiency, increasing the contractility of the uterus, can provoke premature labor.
High magnesium content
in the body
The main causes of excess magnesium: excess intake; violation of the regulation of magnesium metabolism. An increase in the concentration of magnesium is observed with hyperfunction of the parathyroid glands, thyroid gland, nephrocalcinosis, arthritis, psoriasis, dyslexia (a disorder with a violation of the readable text in children). Magnesia salt when administered orally, even in large doses, does not cause poisoning, but acts only as a laxative. At the same time, with parenteral administration of magnesium sulfate, symptoms of intoxication in the form of general depression, lethargy and drowsiness may be observed. With a significant overdose of magnesium compounds, the risk of poisoning is possible (for example, antacids). Anesthesia occurs when the concentration of magnesium in the blood is 15-18 mg%.
The role of magnesium in the pathogenesis of various diseases of the cardiovascular system
Ischemic Heart Disease (CHD)
It was established that in the post-mortem assessment of magnesium content in patients who died from coronary heart disease, the level of magnesium was lower than in death from other causes. Several studies have shown that in patients who have had a myocardial infarction, magnesium deficiency is more frequently detected, but it is not known if it was the cause or consequence of the disease [8]. In some, although not all, studies have shown an improvement in the survival rate of patients with myocardial infarction during magnesium therapy [9].
A recently completed study assessing the correlation of magnesium levels and sudden cardiac death revealed a significant reduction in the risk of sudden cardiac death with elevated serum magnesium levels, regardless of other factors such as arterial hypertension, diabetes, potassium, heart rate, and the presence of IHD in history. At the same time, the level of magnesium consumption has not been established with the risk of sudden cardiac death [10]. However, in relation to arterial hypertension and IHD, a link has also been established with the serum concentration of magnesium, and not with its consumption [11]. It is revealed that a reduced content of magnesium in drinking water increases the risk of developing cardiovascular diseases (especially IHD) and sudden death [12].
Atherosclerosis and dyslipidemia
There is evidence of a correlation between magnesium deficiency and atherosclerosis. Magnesium deficiency has been shown to be associated with an increase in total cholesterol, low density lipids, triglycerides, a decrease in the activity of lecithin – cholesterol – aminotransferase and lipoprotein lipase, and an increase in the activity of HMC – COA reductase [13]. In several animal experiments, it was shown that the progress of atherosclerosis was slower compared with the control group, regardless of the cholesterol level, against the background of supplemental magnesium intake, even in combination with an atherogenic diet. In some studies among patients with hyperlipidemia, a positive significant effect was obtained in reducing the level of total cholesterol and its atherogenic fractions. In addition, several risk factors, such as hypertension, obesity, and insulin resistance, have a common denominator - magnesium deficiency.
Diabetes
Magnesium deficiency matters in the pathogenesis of diabetes for several reasons: many of the enzymes involved in the process of glycolysis are magnesium-dependent. Both insulin-dependent and non-insulin-dependent diabetes mellitus revealed a deficiency of serum magnesium, intracellularly, as well as an increased excretion in the urine [14]. In addition, it was shown that the degree of diabetes control was directly related to the degree of magnesium deficiency, and the additional intake of magnesium was accompanied by an improvement in the control of diabetes mellitus. However, not all people with diabetes, hypomagnesemia, and its degree varies depending on the type of diabetes and gender [15].
Arterial hypertension
Magnesium deficiency can be important in the pathogenesis of hypertension, another risk factor for coronary heart disease. Magnesium is involved in the activation of the Na – K – ATP pump, and also regulates calcium intake to the cell. Thus, magnesium deficiency can lead to a decrease in the intracellular content of sodium and calcium, an increase in total peripheral resistance and vasospasm, which was established in experimental animal studies.
A number of studies have established a link with the consumption of some macroelements, including magnesium, and arterial hypertension [16]. However, the significance of magnesium in the pathogenesis of hypertension is not completely clear, since in various studies contradictory results were obtained in studying the relationship between consumption, excretion, serum level of magnesium and the degree of arterial hypertension. According to a systematic review, there is currently insufficient data for a final judgment on the relationship between magnesium and hypertension [17].
However, for certain categories of patients with hypertension, a violation of magnesium metabolism definitely matters. In particular, it was found that with a family history of hypertension, a reduced intracellular magnesium content occurs. In addition, the hypotensive effect of supplementation with magnesium was observed in patients with reduced urinary excretion, in contrast to other categories of patients where the hypotensive effect was absent [18].
Patients with a high plasma renin content had a reduced plasma magnesium content and responded better to supplemental magnesium intake. An inverse relationship was established between the level of aldosterone and plasma renin, which indicates that a low level of magnesium is associated with an increase in the activity of the renin – angiotensin – aldosterone system [19].
When satisfactory control of arterial hypertension is achieved, the level of free magnesium is normalized. When taking non-Pallid diuretics with a hypotensive goal, significant hypomagnesia also often occurs. The supplemental intake of magnesium contributes to its elimination, improving the control of hypertension [20].
Coronary artery spasm
Magnesium can be considered a natural blocker of calcium channels, since, as a coenzyme, it participates in the movement of calcium inside the smooth muscle cell and from the outside. The significance of hypomagnesemia in the development of spasm and the effectiveness of intravenous administration of magnesium in its elimination have been confirmed in both in vitro experiments and in vivo. Finally, intravenous administration of magnesium sulfate with vasospastic angina pectoris contributes to the effective elimination of vasospasm, which once again confirms the importance of magnesium deficiency in the development of coronary spasm [21].
Myocardial infarction
The state of magnesium metabolism in the period preceding the development of myocardial infarction is difficult to assess, for obvious reasons: the available data are contradictory. However, it is well established that after myocardial infarction, hypomagnesemia occurs, which persists for up to 6 months. A meta-analysis of several controlled studies showed that, against the background of a magnesium infusion, the mortality rate in the treatment group was 3.8% compared with the control group, where the figure was 8%. The main effect is the elimination of malignant arrhythmias [22, 25]. Most studies have established a correlation between hypomagnesemia and post-infarction ventricular arrhythmias.
Chronic heart failure
The development of hypomagnesemia in heart failure is due to several factors. Due to the increase in extracellular fluid volume and the development of secondary hyperaldosteronism, magnesium absorption is reduced. In addition, non-calcium-preserving diuretics also contribute to the excretion of magnesium. In turn, hypomagnesemia aggravates hyperaldosteronism, which leads to fluid retention, can reduce myocardial contractility, increases vasoconstriction. Hypomagnesemia in combination with hypokalemia contributes to ventricular arrhythmias. However, not all researchers recognize the importance and prevalence of hypomagnesaemia in heart failure, it is unambiguously established that active diuretic therapy leads to hypomagnesaemia and this occurs in more than half of patients [23].
Arrhythmias
Since magnesium is involved in the transport of sodium, potassium and calcium, a change in its concentration affects the exchange of electrolytes and the processes of electrical excitation of the cell. The most well-known relationship of hypokalemia and hypomagnesemia. Increasing the level of magnesium leads to bradycardia, an increase in time and suppression of automatism.
Magnesium deficiency, which is often accompanied by hypokalemia, causes prolongation of the QT interval, depression of the ST segment and low-amplitude T waves. Magnesium combines the membrane-stabilizing effect and properties of a calcium antagonist, reduces the variability of the QT interval, which is an adverse prognostic factor for the development of fatal arrhythmias. In addition, magnesium is able to inhibit sympathetic effects on the heart [24].
The effectiveness of intravenous administration of magnesium in relieving ventricular extrasystoles has been identified for a long time, not only in patients with hypokalemia, but also at normal plasma magnesium levels. Framingham study demonstrated the relationship of hypomagnesemia and increased incidence of ventricular extrasystoles, tachycardia, ventricular fibrillation. In the PROMISE study in the group of patients with hypomagnesaemia, a large lethality and a high frequency of ventricular extrasystole were noted in comparison with the group with normal plasma magnesium levels [25].
For many years, magnesium in the form of sulphate is effectively used in stopping pirouette ventricular tachycardia, its effect is due to inhibition of trace depolarizations and shortening of the QT interval duration [26].
In supraventricular arrhythmias, magnesium infusion often transforms supraventricular tachyarrhythmias (atrial tachycardia, polyfocal atrial tachycardia) into sinus rhythm. However, it is not uncommon for this category of patients to detect hypomagnesemia or the concomitant use of loop diuretics, digoxin, aminoglycosides - drugs that promote hypomagnesemia.
The mechanism of influence on arrhythmias caused by digitalis intoxication remains unclear. Magnesium can work by blocking potassium or calcium channels or restoring the function of a sodium-potassium pump. With digitalis intoxication, hypomagnesemia occurs much more frequently than without it, among patients undergoing therapy with digoxin, every fifth of them show hypomagnesemia. At the same time, the administration of magnesium is effective both in patients with hypomagnesaemia and at normal levels of magnesium [27].
In general, the results of a randomized, multicenter, placebo-controlled, double-blind MAGICA study allowed us to consider magnesium and potassium preparations as the generally accepted European standard in the treatment of arrhythmias in patients with receiving cardiac glycosides, diuretics, antiarrhythmics. The antiarrhythmic effect of magnesium preparations appears after 3 weeks. from the start of treatment and reduces the number of ventricular extrasystoles by 12% and the total number of extrasystoles by 60–70% [24].
Mitral valve prolapse
According to epidemiological studies in patients with mitral valve prolapse, as well as with other congenital connective tissue dysplasia, magnesium deficiency is detected in almost 2/3 of cases, which is associated with impaired collagen synthesis in the presence of magnesium deficiency [28].
Conclusion
Magnesium deficiency can play a significant role in the pathogenesis of coronary artery disease, some types of arrhythmias and sudden cardiac death, but it is unclear how the clinician should use this information in daily practice. However, even with a normal level of magnesium in the plasma, the patient may suffer from hypomagnesemia. Since many of these patients take diuretics for hypertension or heart failure, in many cases it is advisable to join the therapy of potassium-saving diuretics, which also contribute to magnesium retention. In a hospital setting in patients with documented hypomagnesemia, magnesium preparations should be used intravenously, intramuscularly, or orally, depending on the clinical situation [29].
Thus, magnesium preparations play an important role in the management of patients with cardiovascular pathology, primarily due to their ability to favorably influence existing risk factors and reduce the risk of cardiovascular diseases at the population level.
With magnesium deficiency, its additional administration is required at the rate of 10–30 mg per 1 kg of body weight per day for at least 2 months, which is due to the slow saturation of tissue depots. It is impossible to provide such an increased intake of magnesium only by changing the diet. The use of magnesium preparations is necessary [30].
Magnesium sulfate is used for parenteral administration in urgent situations, in some cases it is also used orally, causing diarrhea. For long-term treatment of hypomagnesemia use magnesium-containing drugs: tablets or in the form of a solution.
Currently, there are several drugs containing magnesium for replacement therapy: Magnerot, Panangin, Magne B6, magnesium citrate. The first magnesium preparations had inorganic salts in their composition, of which no more than 5% was absorbed by magnesium, moreover, they often caused diarrhea, since magnesium stimulates intestinal peristalsis. Modern magnesium preparations are much better absorbed and do not cause side effects from the gastrointestinal tract.
Magnesium preparations are used in combination with vitamin B6 (which increases digestibility) with potassium, with orotic acid. Magnesium salt of orotic acid is poorly soluble in water, therefore it has practically no laxative effect, it is well absorbed.
Multivitamin complexes with minerals - an unsuccessful source of magnesium, as the calcium contained in them prevents the absorption of magnesium.
In a laboratory-confirmed state of excess magnesium in the body, magnesium-containing drugs are canceled and calcium-containing drugs are prescribed.
With the accumulation of knowledge and additional research, the range of use of magnesium preparations will undoubtedly expand significantly.
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