【medical-news】Int J Cardiol：第三军医大罗教华等研究发现饮用低矿物质瓶装水增加心血管疾病风险

Although bottled water has become increasingly popular world-wide,few of these products have an optimal mineral profile. More than half (59%) ofthe commercial bottled water consumed world-wide ispurified water, and the remaining 41% is primarily spring or natural mineralwater [1]. Meanwhile, there has been a rapid increase in the installationof seawater desalination facilities in water-stressed countries; post-treateddesalinated water has a very low content of bicarbonate, calcium, and magnesium[2]. Epidemiologic studies have documented an inverse relationship between themineral content, or hardness, of water and cardiovascular disease (CVD)[3,4];however, no experimental studies have assessed this issue to date.Therefore, we conducted an experimental investigation of the relationshipbetween water hardness and CVD risk among both rabbits and young men.

尽管瓶装水在全球范围内愈加流行，但这些产品中的矿物质成分并未达到最佳。全世界市场上超过一半（59%）的瓶装水为纯净水，其余41%主要为泉水或天然矿泉水。同时，一些缺水国家中的海水淡化设施安装迅速增加，处理后的淡化水含有低浓度的碳酸氢盐、钙和镁。流行病学研究发现饮用水的矿物质含量或硬度与心血管疾病（CVD）呈负相关，但至今尚无实验对此问题进行研究。因此，第三军医大学罗教华等人进行了实验，研究在家兔和年轻男性中饮用水硬度与CVD风险之间的关系，结果发现，饮用低矿瓶装水会增加心血管疾病风险。

Five types of water with varying levels of total dissolved solids(TDS)and hardness were used in this study: 1) tap water from Chong-qing City (Tcq)[TDS: 229 mg/L; Hardness (CaCO3): 200.3 mg/L]; 2) tap water from Sanya City (Tsy)(59 mg/L; 30 mg/L); 3) bottled natural water (bNW) (87.2 mg/L; 69.6 mg/L); 4)bottled mineralized water(bMW) (10.9 mg/L; 2.3 mg/L); and 5) bottled purifiedwater (bPW )(1.2 mg/L; 0.8 mg/L). All bottledwaters were purchased from supermarkets.

本项研究选用了5中不同总溶解固体量（TDS）和不同硬度的饮用水：1）重庆市自来水（Tcq），TDS为229 mg/L，硬度（CaCO3）为200.3 mg/L；2）三亚市自来水（Tsy），TDS和硬度分别为59 mg/L和30 mg/L；3）瓶装天然矿泉水（bNW），TDS和硬度分别为87.2mg/L和69.6 mg/L；4）瓶装矿化水（bMW），TDS和硬度分别为10.9 mg/L和2.3 mg/L；5）瓶装纯净水（bPW），TDS和硬度分别为1.2 mg/L何0.8 mg/L。所有瓶装水购自超市。

The first component of the study included 80 male New Zealandrabbits, each of which was given Tcq, bNW, bMW,or bPW for 12 months. Levels ofserum CVD biomarkers were measured and morphological changes of the heart andaortic arch were observed. The second component of the study included 168 youngmen (median age: 22, range: 1 7–33; body mass index: 21.7 ± 2.4), who wererecruited and instructed to drink Tsy, bNW, bMW, or bPW for 30 days; serum CVDbiomarkers were detected at days 0 and 31. The experimental protocol wasapproved by the Institutional Animal Use and Care Committee of the ThirdMilitary Medical University, and the authors certify that they complied withthe Principles of Ethical Publishing in the International Journal ofCardiology.

研究的第一部分将80只新西兰兔分为四组，分别给予Tcq、bNW、bMW或bPW喂养12个月，检测血清CVD生物标志物、心脏和主动脉弓形态学改变。研究第二部分招募168名年轻男性，按要求分别饮用Tsy、bNW、bMW或bPW一个月，研究开始前和结束时检测血清CVD生物标志物。实验方案经第三军医大学研究机构实验动物饲养管理和使用委员会批准。研究者声明本次研究遵循《国际心脏病学》的投稿伦理原则。

Among rabbits, there was no statistically significant difference inwater and food intake, body weight, or lipid and lipoprotein levels by watertype. However, levels of the CVD biomarkers Hcy, hs-CRP, and arginasein the bMW group were significantly higher than other three groups ( Fig. 1D,E, F). In addition, more serious morphological changes in the heart and aorticarch were observed in the bMW and bPW groups compared to the Tcq and bNW groups( Fig.2). In both the bMW and bPW groups, interstitial oedema, localizedhigher acidophily of cytoplasm, focal fibre dissolution, andfracture were observed in the heart, while mucoid degeneration, localizedendothelial cell exfoliation, scattered foam cells, and localizedintimal thickening were observed in the intima of the aortic arch.Additionally, focal mucoid degeneration was observed in the intima of theaortic arch in the bNW group.

新西兰兔实验中，不同饮用水组新西兰兔的水和食物摄入量、体重、脂质和脂蛋白水平没有统计学差异，但bMW组的CVD生物标志物Hcy、hs-CRP和精氨酸酶显著高于其他三组（图1D、E、F）。此外，与Tcq组和bNW组相比，bMW组和bPW组的心脏和主动脉弓形态学改变更严重（图2）。bMW组和bPW组中，心脏中可见间质性水肿、局部细胞质高嗜酸性、病灶区纤维分解和断裂，主动脉弓内膜上可见黏液样变性、局部内皮细胞剥落、分散的泡沫细胞和局部内膜增厚。此外，bNW组的主动脉弓内膜也出现了黏液样变性。

Among young men, the bMW group experienced the largest increase ofTC, LDL, apoAI, apoB, atherosclerosis index (apoB/apoAI),and the largestdecrease of HDL among the four groups (Table 1).Conversely, the bNW group hadthe largest decrease of TC, LDL, apoAI, and apoB. Interestingly, the Tsy groupdemonstrated a great decrease of TC, LDL and HDL but an increase of apoB. Therewas no significant difference between groups with regard to changes in TG. Thelevel of Hcy decreased in the Tsy group, but increased in the other threegroups (Fig. 1A); the bPW group experienced the largest increase, followed bythe bMW group. There was no significant difference between groups with regardto changes in hs-CRP or arginase( Fig. 1B, C).

年轻男性试验中，bMW组的受试者TC、LDL、apoAI、apoB和动脉粥样硬化指数（apoB/apoAI）升高最为显著，其余四组HDL水平下降最为显著（表1）。与之相反，bNW组TC、LDL、apoAI和apoB水平下降最为显著。有趣的是，Tsy组TC、LDL和HDL水平显著降低，但apoB水平显著升高。各组间TG水平没有显著差异。Tsy组Hcy水平显著下降，其他三组中显著增加（图1A），其中bPW组Hcy水平升高最多，其次为bMW组。各组间hs-CRP或精氨酸酶改变没有显著差异。

Elevated level of Hcy was considered an independent risk factor forthe development of CVD [5], C-reactive protein (CRP) appeared to be a strong predictorof future coronary events [6], and arginase was upregulated in vascular disease[7]. In this study, higher levels of Hcy, hs-CRP and arginase in those whodrank bMW and bPW suggest a rising risk of CVD.

Hcy水平升高被认为是CVD发展的一个独立风险因子，而C反应蛋白（CRP）可能是未来冠脉事件的强预测因子，且血管疾病中精氨酸酶也会上调。本项研究中，bMW和bPW组的高Hcy、hs-CRP和精氨酸酶水平提示受试者具有高CVD风险。

Atherosclerosis is the most common cause of CVD. Pathologicallesions observed in the intima of the aortic arch in the bMW and bPW groups,including mucoid degeneration, endothelial cell exfoliation, andfoam cells, are involved in the process of atherosclerosis formation. Moreover,the pathological changes observed in the hearts of rabbits in the bPW and bMWgroups can influence the cardiac functions.

动脉粥样硬化是CVD的最常见原因。bMW和bPW组主动脉弓内膜上观察的病理损害，包括黏液样变性、内皮细胞剥落以及泡沫细胞，均参与动脉粥样硬化形成的过程。此外，bPW和bMW组的新西兰兔心脏上观察到病理改变也会影响心脏功能。

In the WHO discussion about the potential health effects ofnutrients in drinking water, calcium and magnesium remained of interest [8].Both calcium and magnesium are essential elements to human health. Studies havedocumented a reduction in CVD mortality risk with increasing magnesium levelsin drinking water, but the relationship between CVD mortality risk and bothwater hardness and calcium levels is uncertain [9]. Magnesium is closelyinvolved in cardiac and vascular function. In this study, low concentration ofmagnesium in bottled water may explain the pathological and lipid profilechanges that were observed in rabbits and young men, respectively.

在WHO关于饮用水中可能有利于健康的营养素的讨论中，钙和镁作为人体健康必须的元素，仍备受瞩目。已有研究表明，饮用水中镁离子水平升高可降低CVD死亡的风险，但尚无研究阐明水的硬度及钙含量与CVD死亡风险之间的联系。镁与心脏和血管功能显著相关。本项研究中，瓶装水中较低的镁浓度也许可以解释分别在新西兰兔和年轻男性中观察到的病理学和脂质乘风改变。

Interestingly, we found that the bMW group had a more deterioratedlipid profile and higher levels of CVD biomarkers than the bPW group. Duringthe production of bMW, very small amounts of minerals (i.e., KCl and MgSO4) areadded to purified water to improve its taste; therefore, although bMW has aslightly higher magnesium concentration than bPW, it is still a type oflow-mineral water. Given the increased popularity of low-mineral water,enhanced efforts are needed to investigate the public health implications ofremineralized water and water remineralization standards, such as the minimallevels of calcium and magnesium to prevent possible health effects.

有趣的是，研究人员发现bMW组的脂质组成比bPW组更为恶化，且CVD生物标志物水平更高。bMW生产过程中会在纯净水中加入少量矿物质（如KCl和MgSO4），以改善口味，因此尽管与bPW相比，bMW中镁水平略高，但它仍是一种低矿饮用水。随着低矿饮用水的逐渐流行，人们应当对再矿化饮用水以及饮用水再矿化标准的公共卫生意义投入更多的研究，如控制饮用水中钙和镁的水平以预防可能的健康影响。

In summary, we found that consumption of low-mineral bottled water (bMW and bPW) is associated with higher levels of CVD bio-markers, seriouspathological lesions of the heart and aortic arch in rabbits, and increasedlevel of Hcy and deteriorated lipid profile in young men. To the best of ourknowledge, this is the first experimental evidence that drinking low-mineralbottled water may increase the risk of CVD in both rabbits and human studies.

总体而言，研究发现饮用低矿物质瓶装水（bMW和bPW）与CVD生物标志物水平升高、新西兰兔心脏和主动脉弓的严重病理损害以及年轻男性Hcy水平升高及脂质组成恶化相关。本项研究首次证明了低矿物质瓶装水可以增加新西兰兔和人CVD风险。