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A systematic review and meta-analysis of prospective studies that comprised 313,041 individuals and 11,995 cardiovascular diseases, 7534 ischemic heart diseases, and 2686 fatal ischemic heart disease events found that higher serum levels of magnesium were significantly associated with a lower risk of cardiovascular disease, and higher dietary magnesium intakes (up to approximately 250 mg/day) were associated with a significantly lower risk of ischemic heart disease caused by a reduced blood supply to the heart muscle.
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Circulating serum magnesium (per 0.2 mmol/L increment) was associated with a 30% lower risk of cardiovascular disease (RR: 0.70; 95% CI: 0.56, 0.88 per 0.2 mmol/L) and trends toward lower risks of IHD (RR: 0.83; 95% CI: 0.75, 1.05) and fatal ischemic heart disease (RR: 0.61; 95% CI: 0.37, 1.00). Dietary magnesium (per 200 mg/day increment) was not significantly associated with cardiovascular disease (RR: 0.89; 95% CI: 0.75, 1.05) but was associated with a 22% lower risk of ischemic heart disease (RR: 0.78; 95% CI: 0.67, 0.92). The association of dietary magnesium with fatal ischemic heart disease was nonlinear (p < 0.001), with an inverse association observed up to a threshold of ~250 mg/day (RR: 0.73; 95% CI: 0.62, 0.86), compared with lower intakes . ½Û´Ä·ìÀ¶¥Þ¥°¥Í¥·¥¦¥à¡Ê0.2mmol / LÁý²Ã¤¢¤¿¤ê¡Ë¤Ï¿´·ì´É¼À´µ¤Î¥ê¥¹¥¯¤ò30¡óÄã²¼¤µ¤»¡¢¤½¤·¤Æ¡¢µõ·ìÀ¿´¼À´µ(IHD)¤ÈÃ×̿Ū¤Êµõ·ìÀ¿´¼À´µ¤ËØí´µ¤¹¤ë¥ê¥¹¥¯¤ò²¼¤²¤ë·¹¸þ¤¬¤¢¤ê¤Þ¤¹¡£
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¿©»ö¤Ë¤è¤ë¥Þ¥°¥Í¥·¥¦¥à¤ÈÃ×̿Ūµõ·ìÀ¿´¼À´µ¤È¤Î´ØÏ¢¤ÏľÀþ¤Ç¤Ï¤Ê¤¯¡¢¤è¤êÄ㤤ÀݼèÎ̤ËÈæ³Ó¤¹¤ë¤È¡¢µÕÁê´Ø¡ÊµÕÈæÎã¡Ë¤ÏÌó250 mg /Æü¤ÎïçÃÍ¡Êʬ´ôÅÀ¡Ë¤Þ¤Ç´Ñ»¡¤µ¤ì¤Þ¤·¤¿¡£ ¡Ê£±Æü¤Ë¿©»ö¤Ë´ó¤ë¥Þ¥°¥Í¥·¥¦¥à¤ÎÀݼèÎ̤¬¶Ë¾¯Î̤ξì¹ç¡¢¸ú²Ì¤¬Ìµ¤¤¤È¸À¤¦¤³¤È¡£¡Ë In a monocentric, controlled, double-blind study, 79 patients with severe congestive heart failure (NYHA IV) under optimal medical cardiovascular treatment were randomised to receive either magnesium orotate (6000 mg for 1 month, 3000 mg for about 11 months, n = 40) or placebo (n = 39). Both groups were comparable in demographic data, duration of heart failure and pre- and concomitant treatment. After mean treatment duration of 1 year (magnesium orotate: 364.1 +/¡Ý 14.7 days, placebo: 361.2 +/¡Ý 12.7 days) the survival rate was 75.7% compared to 51.6% under placebo (p < 0.05). Clinical symptoms improved in 38.5% of patients under magnesium orotate, whereas they deteriorated in 56.3% of patients under placebo (p < 0.001) . ñ¿´ÂÐ¾ÈÆó½ÅÌÕ¸¡»î¸³¡ÊÃ𣱡ˤǡ¢ºÇŬ¤Ê°å³ØÅª¿´·ì´É¼£ÎŤò¼õ¤±¤Æ¤¤¤ë½Å¾Éݵ·ìÀ¿´ÉÔÁ´¡ÊNYHA IV¡Ë´µ¼Ô79¿Í¤ËÂФ·¡¢Ìµºî°Ù¤Ç¡¢40¿Í¤ËÂФ·¤Æ¤Ï¥ª¥í¥Á¥ó»À¥Þ¥°¥Í¥·¥¦¥à¤ò1¥ö·î6000 mg¤Î¥±¡¼¥¹¤ÈÌó11¥ö·î3000 mg¤Î¥±¡¼¥¹¤Ëʬ¤±ÅêÍ¿¤·¡¢»Ä¤ê¤Î39¿Í¤ËÂФ·¤Æ¤ÏÀ®Ê¬¤òÁ´¤¯´Þ¤Þ¤Ê¤¤µ¶Ìô¡Ê¥×¥é¥»¥Ü¡Ë¤òÅêÍ¿¤·¤Þ¤·¤¿¡£
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Magnesium orotate may be used as adjuvant therapy in patients on optimal treatment for severe congestive heart failure, increasing survival rate and improving clinical symptoms and patient¡Çs quality of life.
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A meta-analysis of seven prospective trials with a total of 241,378 participants observed a modest but statistically significant inverse association between magnesium intake and risk of stroke. An intake increment of 100 mg Magnesium/day was associated with an 8% reduction in risk of total stroke (combined RR: 0.92; 95% CI: 0.88, 0.97). Magnesium intake was inversely associated with risk of ischemic stroke (RR: 0.91; 95% CI: 0.87, 0.96) but not intracerebral hemorrhage (RR: 0.96; 95% CI: 0.84, 1.10) or subarachnoid hemorrhage (RR: 1.01; 95% CI: 0.90, 1.14) . In an updated meta-analyses of prospective studies to date, the combined RR of total stroke was 0.87 (95% CI: 0.83, 0.92) for a 100 mg/day increase in magnesium intake, 0.91 (95% CI: 0.88, 0.94) for a 1000 mg/day increase in potassium intake, and 0.98 (95% CI: 0.94, 1.02) for a 300 mg/day increase in calcium intake . ¹ç·×241,378¿Í¤Î»²²Ã¼Ô¤Ë¤è¤ë7¤Ä¤ÎÁ°¸þ¤»î¸³¤Î²òÀϤǤϡ¢¥Þ¥°¥Í¥·¥¦¥àÀݼèÎ̤ÈÇ¾Â´Ãæ¤Î¥ê¥¹¥¯¤È¤Î´Ö¤ËÃæÄøÅ٤Ǥ¹¤¬Åý·×Ū¤ËͰդʵÕÁê´Ø¤ò´Ñ»¡¤·¤Þ¤·¤¿¡£¡ÊÃí¡Ë¤Ä¤Þ¤ê¡¢¥Þ¥°¥Í¥·¥¦¥à¤ò¿¤¯Àݼ褹¤ë¤È¡¢Ç¾Â´Ãæ¤Î¥ê¥¹¥¯¤¬¸º¤ë¤È¤¤¤¦¤³¤È¡£
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Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. In a recent study, 1700 patients with suspected stroke received either intravenous magnesium sulfate or placebo, beginning within 2 h after symptom onset. Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 h after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days .
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Æþ±¡Á°¤Îβ»À¥Þ¥°¥Í¥·¥¦¥à¼£ÎŤγ«»Ï¤Ï°ÂÁ´¤Ç¤¢¤ê¡¢Ç¾Â´Ãæ¾É¾õ¤Îȯ¾É¸å2»þ´Ö°ÊÆâ¤Ë¼£ÎŤò³«»Ï¤¹¤ë¤³¤È¤ò²Äǽ¤Ë¤·¤Þ¤·¤¿¤¬¡¢¤½¤ì¤Ï90ÆüÌܤξ㳲¼£ÎÅ·ë²Ì¤ò²þÁ±¤·¤Þ¤»¤ó¤Ç¤·¤¿¡£ In hemodialysis patients, low magnesium status is associated with other risk factors for cardiovascular disease such as greater incidence of intradialytic hypotension, poorer hemodialysis adequacy, deteriorating calcium-phosphate metabolism, inflammation and carotid intima-media thickness . ·ì±ÕÆ©ÀÏ´µ¼Ô¤Ë¤ª¤¤¤Æ¡¢Äã¥Þ¥°¥Í¥·¥¦¥à¾õÂ֤ϡ¢Æ©ÀÏÃæÄã·ì°µ¤ÎȯÀ¸Î¨¤Î¾å¾º¡¢·ì±ÕÆ©ÀϤÎŬÀÚÀ¤ÎÄã²¼¡¢¥ê¥ó»À¥«¥ë¥·¥¦¥àÂå¼Õ¤Î°²½¡¢±ê¾É¡¢ðôư̮ÆâËìÃæËìÈî¸ü¤Ê¤É¡£¿´·ì´É¼À´µ¤Î¾¤Î´í¸±°ø»Ò¤È´ØÏ¢¤·¤Æ¤¤¤Þ¤¹¡£ Cardiac arrhythmias are well known to be associated with hypomagnesaemia, although the contribution of hypomagnesaemia to its pathogenesis is not fully known due to coexisting hypokalaemia and other electrolyte disturbances. Possible effects of magnesium in preventing cardiac arrhythmias are stabilization of electrolyte concentrations of the heart muscle cell and membranes, calcium antagonism,,elevation of cell energy niveau, improvement in O2 utilisation and diminishing of neurotransmitter release, e.g..adrenaline or noradrenaline. Magnesium depletion increases susceptibility to arrhythmogenic effects of drugs such as cardiac glycosides. The spectrum includes supraventricular and ventricular arrhythmias. Magnesium has a well-established role in the management of torsade de pointes. Torsade de pointes, a repetitive polymorphous ventricular tachycardia with prolongation of QT intervals, has been reported in cases of hypomagnesaemia, and this and other arrhythmias have been successfully treated with intravenous magnesium. In the recent guideline of the American Heart Association and the American College of Cardiology for prevention and treatment of torsade de pointes, tachycardia administration of magnesium and potassium is advised .
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The frequency of cardiac arrhythmias occurring after myocardial infarction is higher in hypomagnesemic patients and can be reduced by magnesium administration. Several trials indicate that an intravenous magnesium infusion early after suspected myocardial infarction could decrease the risk of death. A meta-analysis with 2316 patients of the Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) found a significant reduction in mortality in those patients who were given intravenous magnesium sulfate (8 mmol over 5 min followed by 65 mmol over 24 h) within 24 h of suspected myocardial infarction or physiological saline. By intention-to-treat analysis mortality from all causes was 7.8% in the magnesium group and 10.3% in the placebo group (2 p = 0.04), a relative reduction of 24% (95% confidence interval 1%–43%) . However, another study involving 58,050 patients with suspected myocardial infarction, (ISIS-4, Fourth International Study of Infarct Survival), showed no benefit from magnesium therapy . Also in the Magnesium in Coronaries (MAGIC) trial with 6213 patients with acute ST-elevation myocardial infarction, magnesium therapy had no benefit . Thus, the use of intravenous magnesium sulphate remains controversial. Nevertheless, magnesium therapy should be considered in those with refractory arrhythmias.
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7.2. Cardiovascular Disease
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£·¡¥£²¡¥£±¡£¹â·ì°µ A substantial body of epidemiological and experimental research is linking magnesium deficiency and cardiovascular diseases such as hypertension and atherosclerosis .Hypertension is a major risk factor for heart disease and stroke. Magnesium is involved in blood pressure regulation. Every modification of the endogenous magnesium status leads to changes in vascular tonus and, as a consequence, changes in arterial blood pressure
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Furthermore, alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium-binding proteins.
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The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels, and binding to the membrane. In cell membranes and in lymphocytes of hypertensive patients, our group showed significant increase of calcium, decrease of magnesium and an increased calcium/magnesium ratio (Ca2+/Mg2+ >2) . ³°Ëì¤ò²£Àڤ륫¥ë¥·¥¦¥à¤ª¤è¤Ó¥Þ¥°¥Í¥·¥¦¥à¤Îή¤ì¤Ï¡¢¥«¥ë¥·¥¦¥à¥Ý¥ó¥×¡Ê¥«¥ë¥·¥¦¥à - ¥Þ¥°¥Í¥·¥¦¥à - £Á£Ô£Ð¥¢¡¼¥¼¡Ë¡¢¥«¥ë¥·¥¦¥à¥Á¥ã¥Í¥ë¡¢¤ª¤è¤ÓËì¤Ø¤Î·ë¹ç¤Ë¤è¤Ã¤ÆÄ´Àᤵ¤ì¤Þ¤¹¡£
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Magnesium is a natural calcium antagonist and modulates vasomotor tone, blood pressure, and peripheral blood flow. Its actions as an antihypertensive, antidysrhythmic, anti-inflammatory and anticoagulant agent can be of benefit in the prevention and treatment of cardiovascular diseases. Recent experimental studies with Wistar rats reveal that short magnesium deficiency is associated with a downregulation of telomerase in left ventricular, right ventricular, atrial and aortic muscle cells.Furthermore a deficiency of magnesium resulted in these animal models in a 7–10 fold increased formation of 8-OH-dG in the cardiac and aortic muscle cells, and furthermore the magnesium deficiency is linked to an increased upregulation on neutral-sphingomyelinase
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Epidemiological studies have reported that serum and dietary magnesium are associated inversely with risk factors for coronary heart disease such as hypertension, type 2 diabetes mellitus, and the metabolic syndrome. Additional evidence from ecologic, clinical, and autopsy studies has shown higher magnesium to be potentially protective against sudden cardiac death. ±Ö³ØÅª¸¦µæ¤Ï¡¢·ìÀ¶ÃæµÚ¤Ó¿©»ö¤Ë¤è¤ë¥Þ¥°¥Í¥·¥¦¥à¤¬¡¢¹â·ì°µ¡¢2·¿ÅüǢɡ¢¤ª¤è¤Ó¥á¥¿¥Ü¥ê¥Ã¥¯¥·¥ó¥É¥í¡¼¥à¤Ê¤É¤Î´§¾õư̮À¿´Â¡ÉÂ¤Î´í¸±°ø»Ò¤ÈµÕ¤Î´Ø·¸¤Ë¤¢¤ë¤³¤È¤òÊó¹ð¤·¤Æ¤¤¤Þ¤¹¡£
À¸ÂÖ³ØÅª¡¢Î×¾²Åª¡¢¤ª¤è¤Ó˶¸¡¤Î¸¦µæ¤«¤é¤ÎÄɲäξڵò¤Ï¡¢¤è¤ê¹â¤¤¥Þ¥°¥Í¥·¥¦¥à¤¬¿´Â¡ÆÍÁ³»à¤ËÂФ·¤ÆÀøºßŪ¤ËÊݸîŪ¤Ç¤¢¤ë¤³¤È¤ò¼¨¤·¤Þ¤·¤¿¡£ The Atherosclerosis Risk in Communities (ARIC) Study assessed risk factors and levels of serum magnesium in a cohort of 7887 women and 6345 men aged 45–64 years. After an average of 12 years of follow-up, individuals in the highest quartile of the normal physiologic range of serum magnesium (≥0.88 mmol/L) had an almost 40% reduced risk of sudden cardiac death compared with individuals in the lowest quartile (≤0.75 mmol/L) (HR: 0.62, 95% CI: 0.42–0.93) . Ãϰè¤Ë¤ª¤±¤ë¥¢¥Æ¥í¡¼¥àÀư̮¹Å²½¾É¥ê¥¹¥¯¡ÊARIC¡Ë»î¸³¤Ç¤Ï¡¢45〜64ºÐ¤Î½÷À7887¿Í¤ÈÃËÀ6345¿Í¤Î¥³¥Û¡¼¥È¡Ê½¸ÃĤδѻ¡Åª¸¦µæ¡Ë¤Ë±÷¤±¤ë´í¸±°ø»Ò¤È·ìÀ¶¥Þ¥°¥Í¥·¥¦¥àÇ»ÅÙ¤¬É¾²Á¤µ¤ì¤Þ¤·¤¿¡£
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°ìÆüÀݼè¥Þ¥°¥Í¥·¥¦¥à¤ÎºÇÄã»Íʬ°Ì¿ô¡Ê<261 mg /ÆüÂÐ> 345 mg /Æü¡ËµÚ¤Ó·ìÞù¥Þ¥°¥Í¥·¥¦¥àÇ»ÅÙ¡Ê<0.78 mmol / LÂÐ> 0.86 mmol / L¡Ë¤ÈÈæ³Ó¤·¡¢ºÇ¤â¹â¤¤½÷À¤Ï37¡ó¡Ê ÁêÂХꥹ¥¯¡§0.63¡¢95¡óCI¡§0.44¡¢0.91¡ËµÚ¤Ó77¡ó¡ÊÁêÂХꥹ¥¯¡§0.23¡¢95¡óCI¡§0.09¡¢0.60¡Ë¤â¿´Â¡ÆÍÁ³»à¤Î¥ê¥¹¥¯¤¬¤½¤ì¤¾¤ìÄ㤫¤Ã¤¿¤Î¤Ç¤¹¡£ In the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, another prospective population-based cohort study with 7664 adults aged 20–75 years from The Netherlands found that low urinary magnesium excretion levels (a marker for low dietary magnesium intake) are associated with a higher risk of ischemic heart disease over a median follow-up period of 10.5 years . ¿Õ¡¤ª¤è¤Ó·ì´É¤ÎËö´ü¼À´µ¤ÎͽËÉ¡ÊPREVEND¡Ë¸¦µæ¤Ç¤Ï¡¢¥ª¥é¥ó¥À¤Î20〜75ºÐ¤Î7664¿Í¤ÎÀ®¿Í¤òÂоݤȤ·¤¿Ê̤ÎÁ°¸þ¤¤ÊÃϰ轸Ãĸ¦µæ¤¬¸«¤Ä¤«¤ê¤Þ¤·¤¿¡£
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7. Magnesium in the Treatment and Prevention of Diseases
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Magnesium deficiency has been linked to atherosclerosis, alterations in blood lipids and blood sugar, type 2 diabetes, myocardial infarction, hypertension, kidney stones, premenstrual syndrome and psychiatric disorders . A number of common clinical symptoms and diseases in association with magnesium deficiency are described in the following.
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