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译作分享|镁在高血压和心血管疾病中的作用

2023年02月09日

译作分享

The Role of Magnesium in Hypertension and Cardiovascular Disease

镁在高血压和心血管疾病中的作用

Mark Houston, MD, MS

From the Division of Human Nutrition, Saint Thomas Medical Group and Hospital, Vanderbilt University School of Medicine, Hypertension Institute, Nashville, TN

Magnesium intake of 500 mg ⁄ d to 1000 mg ⁄ d may reduce blood pressure (BP) as much as 5.6 ⁄ 2.8 mmHg. However, clinical studies have a wide range of BP reduction, with some showing no change in BP. The combination of increased intake of magnesium and potassium coupled with reduced sodium intake is more effective in reducing BP than single mineral intake and is often as effective as one antihypertensive drug in treating hypertension. Reducing intracellular sodium and calcium while increasing intracellular magnesium and potassium improves BP response. Magnesium also increases the effectiveness of all antihypertensive drug classes. It remains to be conclusively proven that cardiovascular disease such as coronary heart disease, ischemic stroke, and cardiac arrhythmias can be prevented or treated with magnesium intake. Preliminary evidence suggests that insulin sensitivity, hyperglycemia, diabetes mellitus, left ventricular hypertrophy, and dyslipidemia may be improved with increased magnesium intake. Various genetic defects in magnesium transport are associated with hypertension and possibly with cardiovascular disease. Oral magnesium acts as a natural calcium channel blocker, increases nitric oxide, improves endothelial dysfunction, and induces direct and indirect vasodilation.

每日摄入镁500mg至1000mg可降低血压（BP）5.6/2.8mmHg。然而临床研究中对血压降低范围的定义较广，有些研究中称血压无变化。增加镁和钾的摄入量，同时减少钠的摄入量比摄入单一微量元素更有效，且与单一降压药的治疗效果相近。降低细胞内的钠和钙，同时组合增加细胞内镁和钾，可改善血压反应。镁同时还可提高所有类别的降压药的有效性。通过摄入镁来预防和治疗冠心病、缺血性中风和心律失常等心血管疾病尚缺有力的证据。而初步证据表明，胰岛素敏感性、高血糖、糖尿病、左心室肥大及血脂异常可能随着镁摄入量的增加而得到改善。多种镁转运相关的基因缺陷与高血压有关，且可能伴随心血管疾病。口服镁作为天然钙通道阻断剂，可提高一氧化氮，改善内皮功能紊乱，并直接或间接诱导血管舒张。

Hypertension remains the leading cause of cardiovascular disease (CVD), affecting approximately 1 billion individuals worldwide.¹ More than 72 million Americans, or nearly 1 in 3 adults, are estimated to have high blood pressure (BP), but only 35% reach goal BP control.² Nearly 70 million more adults are at risk for developing prehypertension, and 90% of adults will probably develop high BP by the age of 65, especially systolic hypertension.³ Hypertension is associated with an increased risk of morbidity and mortality from cerebrovascular accidents (CVA), coronary heart disease (CHD), congestive heart failure, and end-stage renal disease (ESRD). Due to its high prevalence, hypertension remains the most common reason for visits to physician’s offices and the primary reason for prescription drug use in the United States.

高血压仍然是心血管疾病（CVD）的主要原因，影响着全世界大约10亿人的健康。¹据估计，超过720万美国人或1/3成年人患有高血压，但只有35%的人达到血压控制的目标。²还有近7000万成年人有患高血压前期的风险，90%的成年人到65岁时可能会出现高血压，尤其是收缩期高血压。³高血压与脑血管意外（CVA）、冠心病（CHD）、充血性心力衰竭及终末期肾病（ESRD）的发病和死亡风险增加密切相关。在美国，由于其高发病率，高血压仍然是美国人就诊的最常见原因和服用处方药的主要原因。

DIET IN THE PREVENTION AND TREATMENT OF HYPERTENSION

饮食在预防和治疗高血压中的作用

Several epidemiologic studies suggest that diet plays an important role in determining BP.^4–6 Dietary therapies known to lower BP include reduced sodium intake, increased potassium and magnesium intake, possibly an increase in calcium intake, and a diet rich in fruits and vegetables.^4–6 The landmark Dietary Approaches to Stop Hypertension (DASH) trial demonstrated that modification of diet significantly lowered BP in patients with stage 1 hypertension and high-normal BP.^7,8 The DASH diet, which emphasizes the consumption of fruits, vegetables, high fiber, and low-fat dairy products, also lowers BP in persons with isolated systolic hypertension (ISH).⁹These BP-lowering effects were seen in 8 weeks and were sustained throughout the study period. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines as well as the recent American Heart Association (AHA) recommendations for the prevention and management of CVD and numerous other international organizations also recognize the role that various foods, macronutrients, micronutrients, and minerals play in lowering BP.^10,12–14

流行病学研究表明，饮食在决定血压方面起重要作用。^4-6已知的可降低血压的饮食疗法包括：减少钠的摄入，增加钾和镁的摄入，也可能增加钙的摄入，并摄入丰富的水果和蔬菜。^4-6具有里程碑意义的“控制高血压的饮食疗法”（DASH）试验表明，改变饮食可以明显降低I期高血压和高/正常血压患者的血压。^7-8 DASH饮食强调食用水果、蔬菜、高纤维和低脂乳制品，也可以降低单纯收缩期高血压（ISH）患者的血压。⁹降压效果在8周内可见，且在整个研究期间持续可见。美国国家预防、检测、评估和治疗高血压联合委员会第七次报告（JNC 7）指南及美国心脏协会（AHA）最近关于预防和管理心血管疾病的建议和多个其他国家组织也确认了各类食物、宏量营养素、微量营养素和矿物质在降低血压方面的作用。^10,12–14

EFFECT OF MAGNESIUM ON BP

镁对血压的影响

Epidemiologic, observational, and clinical trial data show that a diet high in magnesium (at least 500–1000 mg ⁄ d) lowers BP, but the results are inconsistent.^15–17These varied results may relate to the population studied, duration of the trial, use of concomitant drugs, other nutrients and minerals, type and dose of magnesium administered, pretreatment magnesium level, pretreatment BP level, inadequate monitoring for adherence, use of varied measures of serum magnesium, intracellular magnesium, or 24-hour urinary magnesium excretion, as well as lack of evaluation of baseline plasma renin activity, essential fatty acid status, and genetic magnesium transporter status. In most epidemiologic studies, an inverse relationship has been shown between dietary magnesium intake and BP.^15–17

流行病学、观察性和临床试验数据显示，高镁饮食（至少500-1000mg/日）可降低血压，但效果并不一致。^15-17 原因可能与所研究人群、试验持续时间、使用的伴随药物、其他营养素及矿物质、使用的镁剂类型及剂量、治疗前的镁水平、治疗前的血压水平、对依从性的监督不足、对血清镁的多种不同的检测方式、细胞内镁、或24小时尿镁排泄量，同时还缺乏对基线血浆肾素活性、必需脂肪酸状态、及镁转运状态的相关基因评估等有关。在多数流行病学研究中，饮食中镁摄入量与血压之间呈现出反比关系。^15–17

In a study of 60 patients with hypertension given magnesium oxide at 20 mmol⁄d during 8 weeks, significant reductions in ambulatory, home, and office BP were observed.¹⁸The office BP fell by 3.7⁄1.7 mmHg, 24-hour ambulatory BP was reduced by 2.5⁄1.4 mmHg, and home BP decreased by 2.0⁄1.4 mmHg. The levels of serum and urinary magnesium correlated with the BP reduction. Patients with the highest BP levels at entry had the largest reduction in BP.

一项为期8周的研究中，60名高血压患者每日给药氧化镁20mmol，观察到患者的动态血压、家测血压、诊室血压均显著下降。¹⁸诊室血压降低了3.7/1.7 mmHg，24小时动态血压降低了2.5/1.4 mmHg，以及家测血压降低了2.0/1.4 mmHg。血清和尿液中的镁含量与血压降低呈正相关。入院时，血压水平最高的患者，其血压下降幅度最大。

Witteman and colleagues¹⁹ demonstrated significant decreases in BP in a double-blind placebo-controlled trial of 91 middle-aged to elderly women with mild to moderate hypertension using magnesium asparate-HCl (20 mmol/d or 485 mg of magnesium) for 6 months. There was a significant decrease in systolic BP and diastolic BP by 2.7 mmHg (P<.18) and 3.4 mmHg (P<.003), respectively. In addition, BP response was not associated with baseline magnesium level, and patients taking magnesium had a 50% increase in urinary magnesium excretion. In another study of 48 patients with mild uncomplicated hypertension, those given magnesium 600 mg⁄d with lifestyle changes vs those with lifestyle changes only had significant reductions in 24-hour systolic BP and diastolic BP during daytime and nighttime readings of 5.6⁄2.8 mmHg vs 1.3⁄1.8 mmHg (P<.001 and P<.002, respectively), increased serum and intracellular magnesium, increased urinary magnesium excretion, and decreased intracellular calcium and sodium levels.²⁰ Magnesium supplementation (with calcium and potassium) was administered to 96 patients with hypertension during 6 months by Sacks and colleagues²¹ but no significant reduction in BP was noted.

Witteman等人¹⁹ 在一项为期6个月的双盲安慰剂对照试验中证明，91名患有轻度至中度高血压的中年至老年妇女在试验期间使用盐酸镁（20 mmol/日或485 mg镁），血压显著下降。收缩压和舒张压分别显著下降了2.7mmHg（P＜.18）和3.4mmHg（P＜.003）。此外，血压反应与基线镁水平无关，服用镁的患者尿镁排泄量增加50%。在另一项对48名轻度无并发症高血压患者的研究中，服用镁600mg/日并改变生活方式的患者与只改变生活方式的患者相比，24小时收缩压和舒张压在日间和夜间的读数明显减少，分别为5.6/2.8 mmHg（日间，P＜.001）及1.3/1.8mmHg（夜间，P＜.002），血清镁及细胞内镁水平升高，尿镁排泄量增加，细胞内该和那水平下降。²⁰ Sacks等人²¹ 对96名高血压患者补充镁（含钙和钾），为期6个月，但并未发现血压有明显下降。

Meta-analysis of magnesium supplementation has also revealed conflicting results. A review of 29 studies of magnesium was inconclusive as a result of flaws in methodology but suggested that a negative association of BP with magnesium was not present.²²In contrast, a meta-analysis of 20 randomized clinical trials with a median intake of 15.4 mmol/d of magnesium revealed a dose-dependent BP reduction with magnesium supplementation.¹⁵ A more recent meta-analysis of 105 trials randomizing 6805 participants with at least 8 weeks of follow-up found no evidence that magnesium supplements had any important effect on BP.²³

对补充镁的Meta分析也显示了相互矛盾的结果。在（对29项针对补充镁的研究）一项综合回顾中，由于方法上的缺陷导致未有明确定论，但表明血压与镁的负相关关系并不存在。²²而与之相反，在另一项（对20项随机临床试验）Meta分析中，镁的平均摄入量为15.4mmol/日，显示，补充镁后血压有剂量依赖性的降低。¹⁵ 更近期（对105项试验）的一项Meta分析中，随机调查了6805名参与者，随访持续至少8周，没有证据表明补充镁对血压有任何显著影响。²³

The BP response to magnesium may be dependent in part on the baseline plasma renin activity (PRA), but this has not been verified in subsequent studies.²⁴Seventeen inpatients with untreated uncomplicated mild to moderate hypertension and 8 age-matched controls were given 1.0 g⁄d of magnesium oxide for 2 weeks. The average mean 24-hour BP for both daytime and nighttime readings fell from 104.3 mmHg to 99.5 mmHg (P<.05) while there was no change in BP in the control group. The PRA was significantly higher in the responder group than the non-responder group in those who received the magnesium supplement (P<.05). Magnesium suppresses circulating Na+K+ ATPase inhibitory activity to attenuate vascular tone and lower BP. Other studies have shown that oral magnesium improves borderline hypertension.²⁵

对镁的血压反应可能取决于基线血浆肾素活性（PRA），但该观点未在后续研究中得到验证。²⁴ 17名未经治疗且无并发症的轻至中度高血压住院患者及8名同年龄段参与者的对照实验中，给予实验组氧化镁1.0g/日，持续两周。其日间和夜间的24小时平均血压度数从104.3 mmHg下降到99.5 mmHg（P＜.05），而对照组血压无变化。接受镁补充剂的实验组中，反应组的PRA明显高于无反应组（P＜.05）。镁能抑制循环中的钠钾ATP酶抑制活性，以减弱血管张力并降低血压。其他研究中表明，口服镁可改善边缘性高血压。²⁵

Magnesium may have a more pronounced BP-lower-ing effect when administered with high potassium intake and low sodium intake.^26,27 In a double-blind, randomized, placebo-controlled, crossover trial of 32 weeks’ duration, 37 adults with mild to moderate hypertension (diastolic BP <110 mmHg) were given placebo or potassium 60 mmol⁄d alone or in combination with magnesium 20 mmol⁄d in a crossover design. None of the patients were taking any other medications or supplements. The potassium ⁄ magnesium combination significantly reduced BP (P<.001), but the addition of magnesium to the potassium did not decrease BP further. Other studies suggest that high potassium, high magnesium, and low sodium intake will result in additive reductions in BP²⁷ (Table).

镁与高钾、低钠组合摄入时可使降压效果更显著。^26,27 在一项为期32周的双盲、随机、安慰剂对照、交叉实验中，对37名轻至中度高血压成年患者（舒张压<110 mmHg）设计交叉给予单独安慰剂、或单独给钾、或组合补充镁20 mmol/日。期间所有患者没有摄入任何其他药物或补充剂。钾和镁的组合可显著降低血压（P＜.001），但在补钾基础上提高镁补充剂量并没有进一步降低血压。其他研究中表明高钾、高镁、低钠的摄入对降低血压有加成效果。²⁷ （表）

Magnesium given in conjunction with taurine lowers BP, improves insulin resistance, retards atherogenesis, prevents arrhythmias, and stabilizes platelets.^28,29The actions may be related to the common mechanism of action of magnesium and taurine to reduce intracellular calcium and sodium levels.^28,29 In the World Health Organization’s Coordinated Cardiovascular Diseases and Alimentary Comparison (WHO-CAR-DIAC) study, patients with higher 24-hour urine magnesium ⁄ creatinine and taurine ⁄ creatinine levels had significantly lower cardiovascular risks, including CVA, CHD, and myocardial infarction.²⁹

镁与牛磺酸一起服用可降低血压，改善胰岛素抵抗，延缓动脉粥样硬化，防止心律失常，稳定血小板。^28,29 这些作用可能与镁和牛磺酸降低细胞内钙和钠水平的共同作用机制有关。^28,29在世界卫生组织的协调心血管疾病和饮食比较（WHO-CAR-DIAC）研究中，24小时尿镁/肌酐比及牛磺酸/肌酐比水平较高的患者心血管风险明显降低，包括CVA、CHD和心肌梗死。²⁹

Magnesium is also effective in further reducing BP in stage I hypertension, diabetes mellitus, and pregnancy when coadministered with antihypertensive agents such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, diuretics, b-blockers, methyldopa, and other pharmacologic agents.^30–33 A comprehensive analytic review of 44 human studies of oral magnesium for hypertension showed that magnesium supplements enhanced the BP-lowering effect of antihypertensive medications.³¹

镁在与血管紧张素转换酶抑制剂、血管紧张素受体阻断剂、钙通道阻断剂、利尿剂、b-受体阻断剂、甲基多巴等抗高血压药物联合使用时，也能有效地进一步降低I期高血压、糖尿病和妊娠期血压。^30–33 对44项口服镁治疗高血压人群研究的综合分析回顾表明，镁补充剂增强了降压药物的降压效果。³¹

Magnesium intake is correlated with reductions in CVA, CVD, arrhythmias, insulin resistance, diabetes mellitus, and left ventricular hypertrophy in most^34–38but not all studies.³⁹ In a study of 34,670 women, cerebral infarction was inversely correlated with both magnesium and potassium intake.³⁴Left ventricular hypertrophy and left ventricular mass are lower in patients with higher magnesium intakes.³⁵ In the Atherosclerosis Risk in Communities Study (ARIC), higher serum magnesium and magnesium intake were associated with lower prevalence of hypertension, diabetes, and ischemic CVA during 15 years in both men and women.³⁶ Magnesium intake is also correlated with reductions in serum lipids, hyperglycemia, metabolic syndrome, obesity, insulin resistance, and diabetes mellitus.^37,38

在大多数^34-38但不是所有的研究中显示，镁的摄入与CVA、CVD、心律失常、胰岛素抵抗、糖尿病和左心室肥大的减少呈正相关。³⁹ 在一项对34,670名妇女的研究中，脑梗塞与镁和钾的摄入量呈负相关。³⁴ 镁摄入量较高的患者，左心室肥大和左心室质量的指数较低。³⁵ 在动脉粥样硬化群体的风险研究（ARIC）中，较高的血清镁和镁摄入量与15年间男性和女性的高血压、糖尿病和缺血性CVA的患病率较低密切相关。³⁶ 镁的摄入也与血清脂质、高血糖、代谢综合征、肥胖、胰岛素抵抗和糖尿病的减少呈正相关。^37,38

MECHANISMS OF BP REDUCTION WITH MAGNESIUM

镁的降压机制

One of the mechanisms by which magnesium lowers BP is by acting like a natural calcium channel blocker. Magnesium competes with sodium for binding sites on vascular smooth muscle cells, increases prostaglandin E, binds to potassium in a cooperative manner, induces endothelial-dependent vasodilation, improves endothelial dysfunction in hypertensive and diabetic patients, decreases intracellular calcium and sodium, and reduces BP.^28,29,40 Magnesium is more effective in reducing BP when administered as multiple minerals in a natural form and as a combination with magnesium, potassium, and calcium than when given alone.⁴¹

镁降低血压的机制之一是作为一种天然的钙通道阻断剂。镁与钠竞争血管平滑肌细胞上的结合位点，增加前列腺素E，以合作方式与钾结合，诱导内皮依赖性血管扩张，改善高血压和糖尿病患者的内皮功能障碍，减少细胞内钙和钠，并降低血压。^28,29,40与镁在单一给药时比，镁在以含有多种矿物质的天然物质形式及以与钾钙结合的形式给药时可更有效的降低血压。⁴¹

Magnesium is also an essential cofactor for the delta-6-desaturase enzyme, which is the rate-limiting step for the conversion of linoleic acid (LA) to gamma-LA (GLA).^42–44GLA, in turn, elongates to form DGLA (dihomo-gamma-lineleic acid), the precursor for prostaglandin E1 (PGE1), is both a vasodilator and platelet inhibitor.^42–44 Low magnesium states lead to insufficient amounts of PGE1, causing vasoconstriction and increased BP.^42–44

镁也是δ-6-去饱和酶的重要辅助因子之一，是亚油酸（LA）转化为γ-LA（GLA）的限速步骤。^42–44 GLA转而拉长形成的DGLA（二高-γ-亚麻酸，前列腺素E1（PGE1）的前体）是一种血管扩张剂和血小板抑制剂。^42–44 低镁状态可导致PGE1的数量不足，引起血管收缩和血压升高。^42–44

In addition to BP, magnesium regulates intracellular calcium, sodium, potassium, and pH as well as left ventricular mass, insulin sensitivity, and arterial compliance.^17,20Magnesium also suppresses circulating Na+K+ATPase inhibitory activity that reduces vascular tone.²⁴

除血压外，镁还能调节细胞内钙、钾和PH值，及左心室质量、胰岛素敏感性和动脉顺应性。^17,20 镁还能抑制循环中的钠钾ATP酶的抑制活性，降低血管张力。²⁴

The calcium channel blocker mimetic effect of magnesium results in production of vasodilator prostacyclins and nitric oxide and alters the vascular responses to vasoactive agonists.⁴⁴ These varied biochemical reactions control vascular contraction and dilation, growth and apoptosis, differentiation, and inflammation.⁴⁴ Alterations in magnesium transport systems may predispose patients to hypertension and subsequent cardiovascular disease.^45–48Magnesium efflux and influx transport systems have been well characterized in humans. Magnesium efflux occurs via Na++-dependent and Na++-independent pathways. Magnesium influx is controlled by Mrs2p, SLC41A1, ACDP2, Mag T1, TRPM6, and TRPM7 (melastatin).^45–48 In particular, increased Mg++ efflux through altered regulation of the vascular Na+ ⁄ Mg++ exchanger, and decreased Mg influx due to defective vascular and renal TRPM6 ⁄ 7 expression ⁄ activity may be important.^45–48 TRPM6 is found primarily in epithelial cells. TRPM7 is ubiquitously expressed and is implicated as a signaling kinase involved in vascular smooth muscle cell growth, apoptosis, adhesion, contraction, cytoskeletal organization and migration, and is modulated by vasoactive agents, pressure, stretch, and osmotic changes.⁴⁸ TRPM7 thus alters intracellular magnesium levels through changes in efflux and influx, which may be related to the onset and perpetuation of hypertension.⁴⁸

镁的钙通道阻断剂模拟作用导致血管扩张剂前列环素和一氧化氮的产生，并改变了血管对血管活性受体激动剂的反应。⁴⁴ 这些不同的生化反应控制着血管的收缩和扩张、生长和凋亡、分化和炎症。⁴⁴ 镁运输系统的改变可能使患者容易罹患高血压和随后的心血管疾病。^45–48 人体中镁的外排和流入运输系统已有很详尽的研究描述。镁的外排是通过Na++依赖性和Na++非依赖性途径进行的。镁的流入则是由Mrs2p、SLC41A1、ACDP2、Mag T1、TRPM6和TRPM7控制。^45–48 特别是，通过改变的血管Na+⁄Mg++交换器的调节可使镁外排增加，并由于血管和肾脏TRPM6 ⁄ 7的表达或活性缺陷可导致镁流入减少。^45–48 TRPM6主要存在于上皮细胞。TRPM7普遍表达，是参与血管平滑肌细胞生长、凋亡、粘附、收缩、细胞骨架组织和迁移的信号激酶，并受到血管活性物质、压力、拉伸和渗透性变化的调节。⁴⁸ 因此，TRPM7通过流出和流入的变化改变细胞内的镁水平，高血压的发生和持续可能与其有关。⁴⁸

Research involving new imaging techniques to measure intracellular magnesium, such as P-nuclear magnetic resonance and magnesium-specific ion-selective electrodes, which measure intracellular and extracellular free concentrations of magnesium, and fluorescent probes will further enhance our understanding of the role of magnesium in hypertension.^17,49 Intracellular magnesium such as red blood cell magnesium is a more accurate reflection of total body magnesium stores.

涉及测量细胞内镁的新成像技术的研究，如P-核磁共振和镁特异性离子选择电极，测量细胞内和细胞外游离镁的浓度，以及荧光探针，将进一步提供对镁在高血压中的作用的认知。^17,49 细胞内镁，如：红血球镁，能更准确地反映人体总的镁储存水平。

THE “IONIC HYPOTHESIS” OF RESNICK AND THE ROLE OF MAGNESIUM AND OTHER IONS

Resnick的“离子假说”及镁和其他离子的作用

The ionic hypothesis of hypertension and other metabolic disorders by Resnick⁵⁰is characterized by the following: (1) increased intracellular free calcium and reduced intracellular free magnesium determine the amount of vasoconstriction or vasodilation; (2) an elevated glucose and low-density lipoprotein cholesterol increase the intracellular calcium and ⁄ or lower intracellular magnesium in vascular smooth muscle cells; (3) hypertension, insulin resistance, and type II diabetes mellitus are associated with an increased intracellular calcium and decreased intracellular magnesium, which all respond to weight loss; (4) weight loss also decreases intracellular calcium levels; (5) dietary calcium suppressible hormones such as parathyroid hormone (PTH) and 1,25 vitamin D are vasoactive and promote calcium uptake in vascular smooth muscle cells and cardiac muscle; (6) the higher the PTH concentration, the greater the fall in BP, and the greater the reduction in PTH and 1,25 vitamin D, the greater the BP reduction; (7) individuals with saltsensitive and calcium-sensitive hypertension have elevated intracellular calcium PTH and 1,25 vitamin D, but low intracellular magnesium; (8) dietary calcium reverses abnormal calcium indices and lowers BP; (9) dietary potassium reduces urinary calcium excretion and 1,2 vitamin D plasma levels; and (10) magnesium intake reduces tissue calcium accumulation. Increased intake of magnesium, potassium, and calcium with concomitant reductions in sodium intake may lower BP more effectively than changing the intake of any single mineral.

Resnick⁵⁰ 提出的高血压和其他代谢性疾病的离子假说有如下特点：(1）细胞内游离钙的增加和细胞内游离镁的减少决定了血管收缩或血管扩张的量；（2）葡萄糖和低密度脂蛋白胆固醇的升高使血管平滑肌细胞的细胞内钙和⁄或细胞内镁降低。(3) 高血压、胰岛素抵抗和II型糖尿病与细胞内钙的增加和细胞内镁的降低有关，这些都对减肥有反应；(4) 减肥也会降低细胞内钙水平。(5）饮食中可抑制钙的激素，如：甲状旁腺激素（PTH）和1,25维生素D具有血管活性，促进血管平滑肌细胞和心肌对钙的吸收；（6）PTH浓度越高，血压下降越大，PTH和1,25维生素D减少越多，血压下降越多。（7）盐敏感和钙敏感高血压患者的细胞内钙、PTH和1,25维生素D较高，但细胞内镁含量较低；（8）膳食钙可逆转异常的钙指数，降低血压；（9）膳食钾可减少尿钙排泄和1,2维生素D血浆水平；（10）镁摄入可减少组织钙的积累。增加镁、钾和钙的摄入，同时减少钠的摄入，可能比改变任何单一矿物质的摄入量更有效地降低血压。

CONCLUSIONS

总结

The overall effect of diet on BP is determined by the net contribution of various nutrients on cytosolic-free minerals such as potassium, calcium magnesium, and sodium. Measurements of intracellular magnesium are more indicative of body stores and should be used in conjunction with serum magnesium and urinary magnesium to accurately determine magnesium deficiencies. Consumption of 500 mg to 1000 mg of magnesium may lower BP as much as 2.7 mmHg to 5.6 mmHg systolic and 1.7 mmHg to 3.4 mmHg diastolic as measured by causal office BP readings, home BP measurements, or 24-hour ambulatory BP monitoring. However, the variability in study design and methodology, doses and type of magnesium used, pretreatment magnesium and BP levels, population studied, concomitant sodium, potassium and calcium intake, and other issues make definitive conclusions about the magnitude of BP reduction difficult. Magnesium lowers intracellular sodium and calcium, which enhances BP reduction. Magnesium is a natural calcium channel blocker, blocks sodium attachment to vascular smooth muscle cells, increases vasodilating PGE, binds potassium in a cooperative manner, increases nitric oxide, improves endothelial dysfunction, causes vasodilation, and reduces BP. Some genetic defects in magnesium transport may be causative in hypertension. Combinations of magnesium and potassium with low-sodium intakes are more effective in reducing BP than using single minerals. It is recommended that 1000 mg of magnesium be combined with 4.7 g of potassium and <1.5 g of sodium per day through both diet and supplements to maximize BP reduction.²⁷ Combining magnesium with taurine has additive antihypertensive effects and lowers intracellular sodium and calcium. It is recommended that about 1000 mg to 2000 mg of taurine be added to this regimen. These can be administered separately or as magnesium taurate combinations, which are available from many reptutable nutrition companies and variable doses of 100 mg to 500 mg of magnesium taurate. The use of chelated magnesium with an amino acid is better absorbed and reduces diarrhea. Taurine has a mild diuretic effect, but is otherwise well tolerated without adverse effects. Magnesium should be avoided or used with caution in any patient with renal impairment or patients with neuromuscular disorders. Magnesium has additive antihypertensive effects with all antihypertensive drugs and should thus be routinely administered unless patients have specific contraindications such as renal insufficiency or they are taking medications that could result in magnesium retention. The role of magnesium supplementation in the prevention or treatment of CVD, CHD, CVA, cardiac arrhythmias, insulin resistance, hyperglycemia, diabetes mellitus, left ventricular hypertrophy, and dyslipidemia will require more definitive clinical trials in the future.

饮食对血压的总体影响取决于各类营养素对无胞质矿物质净含量的提供（如钾、钙、镁、钠）。测量细胞内镁含量更能准确说明身体内镁储存量。同时测量血清镁和尿液中的镁含量可更准确的判断镁缺乏症。根据诊室血压读数、家测血压读数或24小时动态血压检测结果，服用500 mg至1000 mg的镁可使收缩压降低2.7mmHg至5.6mmHg，舒张压降低1.7mmHg至3.4mmHg。然而，因多数研究中的设计和方法、使用的镁的剂量和剂型、治疗前镁和血压水平、研究的人群、伴随使用的钠、钾和钙的摄入量及其它问题等，使镁对血压降低的程度和效果难以得出明确的结论。镁能降低细胞内的钠和钙，从而增强血压降低的效果。镁是天然的钙通道阻断剂，阻断钠附着在血管平滑肌细胞上，提高血管扩张剂PGE，以合作方式结合钾，增加一氧化氮，改善内皮功能紊乱，使血管扩张，降低血压。与镁转运相关的基因缺陷可能是高血压的致病因素。与单一矿物质相比，使用镁、钾及低钠摄入的组合对降低血压更有效。建议每天通过饮食及补充剂，摄入1000 mg镁、4.7 g钾及＜1.5 g钠，以最大限度降低血压。²⁷ 镁与牛磺酸的结合具有额外的抗高血压作用，并降低细胞内的钠和钙。建议在（镁+牛磺酸）治疗方案中添加约1000 mg至2000 mg牛磺酸。镁与牛磺酸可分开单独服用也可以牛磺酸镁的组合剂形式服用（牛磺酸镁可从知名的营养素品牌购买），牛磺酸镁的可变剂量为100 mg至500 mg。使用含有氨基酸的螯合镁可更好的吸收和减少腹泻。任何患有肾功能损害的病人或有神经肌肉障碍的病人应避免使用镁或谨慎使用。镁与所有抗高血压药物结合使用具有叠加的抗高血压作用，因此应常规使用，除非患者有特定的禁忌症，如肾功能不全或正在服用可能导致镁潴留的药物。补充镁在预防或治疗心血管疾病、CHD、CVA、心律失常、胰岛素抵抗、高血糖、糖尿病、左心室肥大和血脂异常方面的作用，需要在未来进行更明确的临床试验。

RECOMMENDATIONS

建议

Americans consume 3 to 4 times the sodium and about one third the magnesium and potassium that is recommended by current guidelines. A high intake of potassium, magnesium, and possibly calcium through increased consumption of fruits and vegetables, the DASH diet and supplements, and reduced intake ofsodium are important for the prevention of hypertension and major public health problems such as CVD, CHD, and stroke.

美国人的钠摄入量是目前指南所建议的3到4倍，镁和钾的摄入量则约为建议的三分之一。通过增加食用水果和蔬菜、DASH饮食和补充剂来补充大量的钾、镁及部分钙，同时减少钠的摄入，对于预防高血压和主要的公共健康问题，如：心血管疾病、冠心病和中风非常重要。

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