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(BQ) Part 2 book “Magnesium and pyridoxine fundamental studies and clinical practice “ has contents: Correction of the magnesium deficit, physiological importance of pyridoxine, determination of the magnesium and pyridoxine levels,… And other contents.
Chapter 5 CORRECTION OF THE MAGNESIUM DEFICIT 5.1 MAGNESIUM DIET Correction of magnesium deficiency includes dietary and pharmacological components For the selection of the right diet, one should take into account not only the quantitative content of magnesium in food, but also its bioavailability Thus, fresh vegetables, fruits, fresh herbs (parsley, dill, green onions, etc), and nuts have maximum concentration and bioavailability of magnesium When products are processed for long-term storage (drying, canning, etc), concentration of magnesium decreased only slightly, but its bioavailability falls down sharply That is why in summer, when there is a lot of fresh fruits, vegetables and greens on the menu, both the extent and the incidence of the magnesium deficit is reduced (Fedotova, 2003) This is important to keep in mind in the case of children with ADHD who appear to have a deeper deficit of magnesium during the school classes (from September to May) In summer, ADHD children and their parents display fewer complaints than in autumn, winter and spring Depending on geographic zone, the content of magnesium and of other minerals in one and the same product can fluctuate significantly For example, in wheat bran grown on Russian soil the average levels of magnesium (448 mg/100g; Skurihin, 2002) are lower than those in the wheat bran grown in western Europe (590 mg/100g; Murrau, 1999) The table 5-1 details the average magnesium contents of various foods Table 5-1 The content of magnesium in different food products “*” marks the products particularly rich in magnesium (Murrau, 1999) Product Brown algae, kelp Wheat bran Sesame Pumpkin seeds Sunflower seeds Red wine Germinated wheat grain Soybean Brewer’s yeast Mg-content, mg/100g 760* 590* 540* 535* 420* 258* 250* 247* 231* 110 Ivan Y Torshin and Olga A Gromova Table 5-1 (Continued) Product Watermelon Nuts, almond Mg-content, mg/100g 224* 267* Nuts, different 158-267* Hazelnut Peanuts Walnuts Dry milk serum Greens Oatmeal flakes Beans Brown rice Pea Coconut chips Dried pitted apricots Prunes, Dried Rough bread Apricots, raisins Dates Shrimps Avocados Parsley Garlic Dandelion leaves Bananas Cheese Marine fish White rice Aubergines Meat (beef) Meat (chicken) Milk 184 175 131 180 170 142 130 130 107 90 105 102 90 60 58 51 45 41 36 36 35 30 24-73 27 16 20 19 13 5.2 SOURCES OF MAGNESIUM IN THE ENVIRONMENT Magnesium is present as a major component in nearly 200 different minerals Magnesium chloride and sulphate are also the major components of the dried residue of the sea water and sea bathing is often recommended as a supplementary procedure for correction of magnesium deficiency Normally, absorption of magnesium, iodine, calcium and other minerals from seawater through skin and mucus is insignificant but it grows observably when the patient has deficiency of magnesium Therefore, sea bathing and mud bathing, along with inhalations of the sea water, somewhat help in restoration of the mineral balance in the course of treatment of cervical erosion, chronic tonsillitis, bronchial asthma and other diseases The content of the soluble salts of magnesium and calcium determine the hardness of the drinking water of a particular region Magnesium is also present in the crude salt as well as in salts from specific natural deposits: Black Indian salt, Salzburg salt, Bishofit from Ural, Hungarian salt, Saxon salt, Irish salt (of the Saga type), Greek salt etc Correction of the Magnesium Deficit 111 Of great importance for the magnesium correction is the treatment with mineral water that contains adequate supply of magnesium Since ancient times it was noticed that the incidence of cardiovascular disease and of many others diseases tends to be higher in certain regions which were later found to be impoverished in minerals and trace elements The residents of mega-cities often receive water with the addition of chlorine, fluorine and other special components from the water-cleansing columns Many of these chemical components adversely affect the balance of magnesium, potassium and calcium It should be noted, however, that most of the commercially available mineral waters are not very high in magnesium and mineral waters naturally high in magnesium (such as Slovenian “Donat”) are not very numerous 5.3 PHARMACOLOGICAL CORRECTION OF MAGNESIUM DEFICIENCY Pharmacological correction of magnesium deficiency is based on regular intake per os of 5-15 mg/kg of magnesium salts for several months and in accordance with age and gender requirements (see tables in Chapter 2) For the correction of magnesium, as it is the case of correction of other mineral deficiencies, bioorganic drugs of different generations can be used It is known for more than half a century that low adsorption, low assimilation and considerable side effects (metal taste in the mouth, nausea, vomiting) are essential drawbacks of the 1st generation of the magnesium drugs During the two last decades, progressive pharmaceutical companies actively elaborate second and subsequent generations of bioorganic drugs and supplements which contain minerals in the form of organic salts, complexes with amino acids and other organic ligands (table 5-2) Table 5-2 Classification of the drugs for the correction of mineral and trace element deficiencies (Gromova, 2003) Generation Composition Examples I Inorganic compositions II Organic compositions Magnesium oxide, magnesium sulphate, zinc oxide, potassium chloride, sodium selenite Magnesium lactate, magnesium pidolate, zinc asparaginate, chromium picolinate, chromium nicotinate Organic salts plus vitamins (magnesium lactate together with pyridoxine), amino acids, alkaloids, bioflavonoids, enzymes, natural pigments like chlorophyll, plant extracts III IV Minerals in combination with biological ligands exogenous natural (plant and animal) and synthetic origin Minerals in conjunction with exoligands, complete analogs of endogenous ligands, “orthomolecular” complexes with neuropeptides, amino acids, enzymes, polysaccharides Extract of Ginkgo Biloba, Se-methionine, Secysteine, Zn-carnosine, Mg-creatinine kinase, Cu -ceruloplasmin, Se-protein,Zn-metallotionein, Mn-containing superoxide dismutase 112 Ivan Y Torshin and Olga A Gromova Organic magnesium salts are better adsorbed, tolerated better by patients, produce less side effects and restitute magnesium deficiency more efficiently (table 5-3, figure 5-1) Table 5-3 Magnesium forms and their bioavailability (NB: during magnesium deficiency, bioavailability of all the forms slightly increases) Magnesium salt Magnesium oxide Magnesium hydroxide Brutto formula MgO Mg(OH)2 Bioavailability 4,7% 5% Generation I Magnesium carbonate Magnesium peroxide Magnesium sulfate MgCO3 3% I MgO2 6% I MgSO4 5% I Magnesium citrate Magnesium asparaginate Magnesium orotate Magnesium lactate Magnesium pidolate С12Н10Mg2O14 С4Н8MgN2O3 37% 32% II II Side effects Dyspepsia Dyspepsia, diarrhea Диспепсия, diarrhea Dyspepsia, diarrhea Dyspepsia, diarrhea Dyspepsia, acute inflammation of gastrointestinal tract N/A N/A С10Н6MgN4O8 38% II N/A С6H10MgO6 38% II N/A С10Н12MgN2O6 43% II N/A Ranade, Somberg (2001) presented the comparative analysis of bioavailability of various salts of magnesium Therapeutically, the magnesium salts constitute a specific class of drugs with quite different pharmacological applications For example, magnesium citrate is used in nephrolithiasis, magnesium hydroxide as an antacid There are several well absorbed galenical forms of magnesium drugs: magnesium citrate, magnesium gluconate, magnesium orotate, magnesium thiosulfate, magnesium lactate (MagneB6 tablets), magnesium pidolate (MagneB6 solution to drink) The contents of elemental magnesium in various forms vary For example, magnesium hydroxide, chewing tablet - 130 mg of elemebtary magnesium; magnesium gluconate, tablet 0.5 g - 27 mg of magnesium; magnesium citrate sparkling tablet 0,15 g - 24,3 mg; magnesium orotate, tablet 0,5 g - 32,8 mg; magnesium thiosulfate, tablet 0,5 g - 49,7 mg; magnesium lactate (Magne B6 tablets, 470 mg) - 48 mg (Ogunyemi, 2007) For magnesium correction, different generations of drugs can be used The first generation include inorganic compositions: magnesium oxide, sulfate, chloride, etc; the the second - organic compounds: magnesium lactate, orotat, pidolat, glitsinat, asparaginate, citrate, ascorbate Pidolate, citrate, gluconate, aspartate are characterized by a higher excretion with urine than inorganic salts (Coudray et al 2006) At the same time, inorganic salts of magnesium are poorly tolerated and more often produce dyspeptic complications such as diarrhea, vomiting, stomach pains (Grimes, Nanda, 2006) Correction of the Magnesium Deficit 113 Figure 5-1 Magnesium bioavailability of inorganic and organic salts Recently proposed “natural” drugs made from crushed animal bone, dolomite, egg shells, oyster shells contain too much harmful impurities and, in particular, lead (figure 5-2) Figure 5-2 Lead impurities in the “natural” magnesium preparations (Blumberg, 2004) 114 Ivan Y Torshin and Olga A Gromova 5.4 PARENTERAL MAGNESIUM THERAPY Parenteral (especially intravenous) therapy with magnesium is indicated in urgent cases of magnesium deficiency as well as in the case when previously used therapy was ineffective The therapeutic forms for the parenteral therapy differ in their efficiency, magnesium content and bioavailability (Durlach, 2004) A comparison of the magnesium gluconate, fumarate and chloride indicated that parenteral infusion of magnesium at concentrations mmol/L would be most optimal from the point of view efficiency and safety (Durlach, 2002) Parenteral magnesiotherapy normalizes the absorption of magnesium Treatment is more efficient if magnesium is introduced along with magnesium fixator such as vitamin B6 or insulin Parenteral therapy must be done in stationary conditions and the usual dosage is 100 mg/hour during the 4-6 hours a day (table 5-4) Table 5-4 Contents of elemental magnesium in pharmaceutical forms for parenteral introduction Preparation Solution Magnesium ascorbate Magnesium glutamate Magnesium sulfate Magnesium ascorbate Magnesium chloride Magnesium sulfate Magnesium sulfate Magnesium diasporal forte 5% injection solution 10 % injection solution 10% intravenous solution 10 % injection solution 20% intravenous solution 25% intravenous solution 50% intravenous solution injection solution, 2ml Elemental magnesium, (mg/ml of solution) 6,1 7,6 9,9 12,2 24 24,75 49,5 320 Before any treatment course of parenteral magnesium therapy, it is necessary to determine the levels of magnesium in plasma and erythrocytes Contraindications for parenteral magnesium therapy include: • • • • severe renal failure; miastenia gravis; malignant neoplasms; urinary tract infection (which accelerates precipitation of the magnesium ammonium phosphates) 5.5 MAGNESIUM-PRESERVING DIURETICS Common diuretics such as furosemide (and, to some extent, indapamide and hypothiazid) accelerate elimination not only of sodium, calcium, potassium and chlorine, but also of a number of important minerals: Se, V, Zn, Ni, Li, as well as Mg (Gromova, Grishina, 2005) This should be taken into account when planning the course of magnesium therapy or when prescribing diuretics Mg-preserving diuretics such as amiloride or aldacton are especially recommended when more than 6mmol of magnesium is excreted in two hours Correction of the Magnesium Deficit 115 5.6 MAGNESIUM FIXATION Vitamin B6, vitamin D and vitamin B1 are the most important fixators of magnesium in the body These fixators can be used immediately upon diagnosis of primary magnesium deficiency and also in the case of ineffective treatment by other drugs • • In pharmacological doses (in the form of pyridoxine hydrochloride), vitamin B6 increases the magnesium in plasma and erythrocytes and reduces magnesium elimination when applied along with a a dose of magnesium Vitamin D in pharmacological doses, either natural (D3 or cholecalcipherol) or synthetic (D2 or ergocaciferol) is used to reduce the risk of acute or chronic hypercalcemia Vitamin D-based therapy in combination with magnesium therapy should take into account three points: o o o • Calcium therapy and phosphate therapy cannot be done simultaneously; In conjunction with magnesium therapy, not pharmacological but physiological does of vitamin D have to be used (200-400 IU/day); Systematic monthly control of calciemia (