1. 盐在生命活动中的基础生理功能
1.1 钠元素的生物化学作用
钠元素（Na+）作为生命活动中至关重要的一种电解质，在所有动物（包括人类）体内发挥着不可或缺的生物化学作用。它不仅是维持细胞正常功能的基础，更是神经系统、循环系统以及体液平衡的关键组分。
首先，钠离子在神经信号传导中扮演核心角色。电压门控钠通道（voltage-gated sodium channels）是神经和肌肉细胞产生动作电位（action potentials）的起始者 1。当细胞膜受到刺激时，这些通道迅速打开，允许钠离子大量内流，从而导致细胞膜去极化，形成神经冲动的快速传播 12。例如，在神经元中，钠离子的流入是动作电位上升阶段的决定性因素，其动力学特性直接影响神经信号的传导速度和模式 23。人类B细胞膜上也存在功能性电压门控钠通道，其敏感性介于TTX敏感和TTX不敏感通道之间，表明B细胞膜上共存多种Na+通道亚型，并可能在维持静息膜电位中发挥作用 4。
其次，钠元素对于维持细胞膜电位和细胞内外渗透压平衡至关重要。细胞膜两侧的钠钾泵（Na+/K+-ATPase）通过主动转运，将钠离子泵出细胞，同时将钾离子泵入细胞，从而维持细胞膜内外的离子浓度梯度，产生静息膜电位 56。这种电位差是神经元、肌肉细胞等兴奋性细胞正常工作的必要条件，也影响着其他多种细胞功能。此外，钠离子是细胞外液中最主要的阳离子，其浓度决定了细胞外液的渗透压。体液渗透压的稳定对于细胞体积的维持至关重要，任何显著的渗透压波动都可能导致细胞肿胀或脱水，影响其正常功能 78。肾脏在维持体钠含量和体液平衡方面起着核心作用，通过调节钠的排泄来维持细胞外液的恒定体积 79。
此外，钠还参与多种其他生理过程。例如，线粒体内钠梯度被发现能够控制哺乳动物线粒体膜电位的一半，这一过程由线粒体Na/H交换器（mNHE）调节，其功能失调与Leber遗传性视神经病（LHON）等神经退行性疾病的分子发病机制相关 10。肾小管中的SLC家族转运蛋白对钠的重吸收至关重要，其调节机制与表观遗传修饰因子SETD2有关，SETD2的失活会导致小鼠低血容量和尿液排泄过多，并降低SLC转运蛋白的表达，这提示肾小管中的代谢与表观基因组之间存在串扰 9。同时，钠的平衡也与血压调节密切相关，血浆中钠离子浓度和渗透压的持续监测由大脑中的独立传感系统完成，以确保体液稳态的维持 11。这些多方面的功能共同说明，所有动物都对钠离子有着绝对的需求。
1.2 盐摄入与代谢平衡的关联
钠的摄入与排泄是一个受严密调控的动态平衡过程，旨在维持体内液体容量、渗透压及血压的稳定。这一平衡主要通过消化道吸收和肾脏的重吸收与排泄机制来调节。
在消化道中，钠的吸收主要发生在小肠和结肠。正常情况下，肠道能够间歇性地从低钠含量的复杂大分子底物中吸收钠。小肠上部对钠离子具有高度渗透性，加上富含钠的唾液和胰胆分泌物，导致大量钠流入肠腔。然而，这些大量的钠内流通过回肠和近端结肠的钠吸收得到平衡，这些部位对钠的渗透性相对较低，但具有主动吸收钠的能力 12。例如，在空肠切除后，回肠对葡萄糖、水和电解质的吸收能力会增强，表现出适应性增加 13。此外，肠道钠-氢交换器3 (NHE3) 在小肠内发挥作用，通过抑制其活性可减少钠吸收，进而影响磷酸盐的跨细胞旁路渗透性 14。
肾脏是维持钠平衡的核心器官，通过精密的重吸收和排泄机制来调节体内的钠含量 15。肾脏对钠的重吸收发生在肾单位的不同节段，包括近端小管、亨利氏袢的粗升支、远曲小管和集合管。
- 近端小管：在糖尿病肾病等情况下，肾小球滤过率升高主要响应于肾小管传递给肾小球的信号：肾小球滤液中高水平的葡萄糖驱动近端小管中的钠-葡萄糖协同转运蛋白SGLT2和SGLT1增加对葡萄糖和钠的重吸收，同时氯化物和水的被动重吸收也增加 16。
- 亨利氏袢的粗升支：抗利尿激素（ADH，也称加压素）通过刺激V2受体，增加亨利氏袢粗升支的钠重吸收，从而调节尿液渗透压 17。
- 远曲小管：远曲小管在钠、钾和二价阳离子稳态中扮演关键角色。最新的研究表明，远曲小管在分子层面调控这些过程 18。
- 集合管：在远端肾单位中，钠转运的调节对液体和电解质稳态至关重要。钠是多种有机和无机溶质继发性主动转运的主要驱动力。在远端肾单位，钠继续在控制体内钠总量及其在细胞内外的浓度方面发挥核心作用 19。
当体内钠水平失衡时，一系列神经-体液调节机制会被激活。其中，肾素-血管紧张素-醛固酮系统（RAAS）是维持血浆钠浓度、动脉血压和细胞外液容量的关键系统 20。当血容量或血压下降时，肾脏分泌肾素，启动一系列反应，最终生成血管紧张素II。血管紧张素II不仅直接作用于血管收缩，还会刺激醛固酮的释放，醛固酮进而促进肾脏对钠和水的重吸收，减少钠的排泄 21。抗利尿激素（ADH）的释放也受体液渗透压和容量变化的调节，它能减少水的流失，从而有助于维持血容量和钠浓度 21。
然而，钠平衡的调控并非完全由肾脏中心模型解释。近期研究指出，钠可以在皮肤和肌肉等组织中进行储存，这与多种疾病（如高血压、慢性肾病、心力衰竭）相关 22。在高盐摄入下，人体可能不会通过增加饮水来平衡钠负荷，而是通过复杂的调控过程（受激素波动、代谢、食物摄入等影响）增加水的潴留，这可能与尿素和肾髓质中尿素转运体的增加有关 23。
总而言之，钠的摄入-排泄动态平衡是一个高度整合的过程，涉及消化道的有效吸收以及肾脏精密的重吸收和排泄，并受到多种激素和神经信号的复杂调控。这种复杂的平衡机制确保了生命活动对钠的持续需求，并为后续分析人类与动物在盐需求和代谢上的差异奠定了生理基础。
2. 人类主动添加盐的演化与文化驱动
2.1 从自然摄盐到主动添加的转变
人类对盐的需求是与生俱来的生理本能，但其获取和使用方式的演变却反映了深刻的文化和技术进步。在漫长的演化历程中，早期人类主要依赖自然食物来获取钠，这一阶段的饮食结构与动物的天然摄取模式有着相似之处。
早期的人类祖先，尤其是从以植物为主的食性向杂食性转变的过程中，开始通过食用肉类、植物以及某些特定矿物质来源来获取钠。例如，捕食动物的血液和组织中含有一定量的钠。在农业出现之前，人类的饮食结构中植物性食物占比较高，导致其从自然饮食中获得的钠相对有限 24。
大约在10,000年前，早期人类的生活方式发生了显著转变，从游牧的狩猎采集者逐渐过渡到定居的村落居民，并开始发展农业。这一转变带来了饮食结构的变化：谷物和蔬菜在膳食中的比重增加，而这些食物的钠含量通常低于肉类 24。这种膳食结构的改变可能加剧了人类从自然食物中获取钠的不足。
火的使用和烹饪技术的出现是人类饮食史上一个里程碑式的事件，它不仅扩大了食物的种类，提高了食物的消化率和能量获取效率，也为人类主动添加盐奠定了基础 2526。通过烹饪，食物的口感和风味得到了显著改善。然而，值得注意的是，烹饪过程本身可能会影响食物中矿物质的含量。例如，煮沸等烹饪方式可能导致蔬菜中钠和钾等矿物质的流失，尽管不同烹饪方法（如蒸、烤、微波）对钠含量的影响各异，且有机种植的蔬菜在某些情况下可能更容易在烹饪中流失钠 27。
在食物保存方面，盐的作用尤为关键。在没有冰箱等现代保鲜技术的时代，早期人类发现盐腌是延长食物保质期的有效方法 24。将食物（特别是肉类）浸泡在盐水中或用盐涂抹，可以抑制微生物生长，防止腐败。这一发现使得人类能够储存食物以备不时之需，从而减少了对每日狩猎或采集的依赖，增强了生存能力 25。这种以盐为基础的食物保存技术，无疑促使盐从一种偶然获得的物质转变为一种被主动寻求和利用的重要资源。例如，亚硝酸钠在肉制品加工中被广泛用作多功能固化剂，赋予产品独特的颜色和风味，并延长保质期，尽管其潜在的健康风险也引发了争议 28。
因此，从自然食物获取钠的局限性、饮食结构的演变、火的利用与烹饪技术的进步，以及对食物保存的需求，共同推动了人类从被动接受自然钠源到主动添加盐的行为转变。这一转变不仅是生理需求的满足，更是人类适应环境、发展文明的重要体现。
2.2 盐的文化与经济属性强化
随着人类社会的发展，盐不仅仅满足了基本的生理需求和食物保存功能，更逐渐获得了深远的文化和经济意义，其地位从一种珍稀的自然资源演变为日常饮食中不可或缺的必需品。
在古代，盐的获取往往受地理条件限制，因此其价值极高，甚至一度充当货币的功能。许多文明都曾使用盐作为交换媒介或支付报酬。在中国，盐的生产和贸易长期以来是国家重要的财政收入来源，盐政制度在历史上扮演了举足轻重的角色。盐的稀缺性和重要性使其成为重要的贸易商品，促进了跨区域的商业往来和文明交流。例如，有研究指出，古典玛雅文明时期（公元600-900年），伯利兹的佩恩斯溪盐场生产的盐和腌制鱼是经济的重要组成部分，这些商品被储存和交易，这与罗马、中国等其他文明中盐和腌制鱼作为食物储存、贸易和国家财政关键组成部分的做法相对应 29。
制盐技术的进步极大地提升了盐的易得性，从而进一步巩固了其在人类饮食中的地位。最初，人类可能通过从含盐植物中提取或从盐泉、盐湖中收集结晶盐。随后，随着技术发展，人们掌握了更高效的制盐方法。例如，海盐的生产依赖于海水蒸发，这可能包括简单的日晒蒸发，或更复杂的煮盐技术。内陆地区则可能通过开采岩盐或利用盐井卤水熬制。这些技术的演进使得盐的产量大幅增加，成本降低，从而使得普通民众也能负担得起盐的消费。当盐变得普及和廉价时，人们开始将其更广泛地应用于烹饪中，以增强食物风味，使其成为日常饮食中不可或缺的调味品。
此外，盐还承载了丰富的文化内涵。在许多文化中，盐象征着纯洁、永恒、友谊和忠诚。在宗教仪式、民间习俗和宴请中，盐常被赋予特殊的象征意义。例如，分享盐被视为建立信任和盟约的标志。这些文化层面的意义进一步强化了盐在人类生活中的地位，使其不仅仅是生理上的需求，更成为了社会交往和文化传承的重要载体。
综上所述，盐从最初的生理必需品，在人类社会演进过程中，逐渐被赋予了货币、贸易商品属性，并伴随着制盐技术的进步而普及，最终通过烹饪和文化习俗的渗透，成为了人类日常饮食中根深蒂固的一部分。这种文化与经济属性的强化，是人类主动添加盐行为得以持续并成为普遍现象的重要驱动力。
3. 动物的盐需求与自然摄取机制
3.1 不同生态位动物的钠获取策略
与人类通过主动添加盐来满足需求不同，动物在长期的演化过程中形成了多样化的自然摄钠策略，以适应其特定的生态位和饮食习惯。这些策略确保了它们在没有人工干预的情况下也能维持钠的生理平衡。
草食动物是典型的钠缺乏风险群体，因为植物体内的钠含量普遍较低，而钾含量相对较高 30。为了弥补这一不足，草食动物发展出了多种获取钠的方式：
- 舔食含盐土壤或矿物舔舐区（Mineral Licks/Kudurs）：这是草食动物最常见的补钠行为之一。它们会主动寻找富含钠及其他矿物质的土壤、岩石或地表沉积物进行舔食 31。例如，在俄罗斯，这些被动物舔食的区域被称为“kudurs”，动物在那里获取的不仅仅是盐，还有许多其他矿物质 31。北美野牛和非洲象等大型草食动物会通过啃食特定区域的土壤来获取钠，这甚至能够改变局部地貌，形成所谓的“放牧草坪（grazing lawns）”，这些草坪能提供稳定的钠源 30。
- 富钠植物的摄取：部分植物在生长过程中能够从土壤中积累较多的钠，草食动物可能会优先选择这些植物。虽然大多数植物的钠含量不高，但一些特定物种或生长在盐碱地的植物可以成为重要的钠来源。
- 水体的钠含量：饮用水源的钠含量也会影响草食动物的钠摄取。在某些地区，地表水或地下水的钠浓度可能足以补充一部分需求。
肉食动物则通过捕食猎物来高效获取钠。由于动物的血液、肌肉和内脏等组织中富含钠，肉食动物在捕食并消化猎物的过程中，能够充分满足自身的钠需求。例如，猫科动物的钠营养研究表明，健康的猫能够通过饮食调整对不同钠含量做出适应，并且在正常情况下不需要额外的钠补充 3233。这意味着，对于典型的肉食动物而言，其自然猎物提供的钠已足够维持生理平衡，无需额外的摄入策略。
水生动物，特别是海洋生物，生活在一个天然富含盐分的环境中，因此它们的钠获取策略与陆生动物截然不同。
- 直接从水体吸收：许多水生动物，特别是鱼类，能够通过鳃等器官直接从周围水体中吸收钠离子。例如，鲤鱼（Cyprinus carpio）能够通过鳃高效吸收水中的离子，并且在重金属胁迫下，会通过诱导Na/K-ATPase等基因的表达来代偿性地维持钠的稳态 34。
- 渗透压调节：海洋硬骨鱼类为了应对高盐环境导致的脱水风险，会主动饮用海水，并通过鳃和肾脏高效排出多余的盐分，同时吸收所需的水和离子，以维持体内渗透压平衡。淡水鱼类则面临钠流失的挑战，它们通过鳃主动吸收钠，并通过肾脏排出大量稀释尿液来保留钠。
总的来说，不同生态位的动物根据其所处的环境和食物来源，发展出了精妙的钠获取机制，这些机制与它们的生理适应性紧密结合，共同构成了它们无需主动加盐也能维持生命活动的基础。
3.2 动物盐代谢的适应性特征
动物在长期演化过程中，为适应各自独特的生存环境和饮食习惯，发展出了一系列特异性的盐代谢适应性特征。这些生理机制使得它们能够在自然状态下有效管理体内的钠水平，从而无需像人类那样主动添加盐来满足需求。
反刍动物的唾液钠循环利用是其对低钠饮食环境的一种显著适应。反刍动物（如牛、羊）的日粮主要由植物组成，而植物的钠含量通常较低。为了维持瘤胃微生物的正常功能（需要稳定的pH和渗透压），反刍动物需要分泌大量富含碳酸氢盐和钠的唾液。在幼年阶段，犊牛的唾液中钠和磷酸盐浓度随时间增长而增加，这表明其唾液腺浓缩矿物质的能力是遵循遗传程序的，而不是受饮食能量摄入影响 35。成年反刍动物每天可分泌高达数百升的唾液。为了避免因唾液分泌而造成的钠大量流失，它们发展出了一种高效的钠循环机制：当钠随唾液进入瘤胃后，大部分钠会与瘤胃内容物一起被吸收，最终返回血液，形成一个有效的钠循环通路 36。此外，在热应激条件下，泌乳牛瘤胃液中的电解质浓度，特别是钠和钾，会下降 37。这种唾液钠的循环利用，确保了在钠摄入不足的情况下，瘤胃环境仍能保持稳定，并最大限度地保留体内有限的钠资源。
海洋哺乳动物的高效排盐肾脏是其适应高盐海洋环境的关键。与陆生哺乳动物不同，海洋哺乳动物生活在海水中，它们常常需要饮用海水或通过捕食海洋生物摄入高盐分。为了应对高盐负荷，它们的肾脏具有卓越的浓缩尿液能力，能够排出比海水更浓的盐溶液，从而有效清除体内多余的盐分并保留淡水 38。例如，海豹和鲸鱼的肾脏结构虽然与陆生哺乳动物有所不同（呈现多肾小叶结构，即“分叶肾”），但这并非赋予其更高的浓缩能力。它们通过代谢水和饮食水维持水平衡，并且仅在少数情况下才会饮用海水。值得注意的是，海獭经常饮用海水，而海牛则频繁饮用淡水，显示出不同海洋哺乳动物在水和电解质平衡策略上的多样性 38。在一些极端情况下，如圈养的海洋鸟类，如果只饲喂淡水，其血清钠和氯化物水平会显著下降，需要额外补充盐分 39。这进一步说明了海洋生物在自然状态下，其生理机制是与高盐环境相适应的。
其他动物的适应性也值得关注：
- 骆驼：作为典型的沙漠动物，骆驼在严重脱水和快速再水合的循环中表现出惊人的适应能力。它们能够承受高达初始体重18-40%的严重脱水，远超大多数单胃哺乳动物。这种能力部分归因于其瘤胃中巨大的水库，其中储存的水分可以被利用，但随之也会带来钠钾负荷。骆驼的肾脏能够有效地“脱盐”从肠道吸收的水分，同时维持唾液流向瘤胃 36。
- 免疫系统与钠平衡：从更广阔的视角来看，动物的营养状况，包括矿物质（如钠、氯）的摄入水平，与免疫功能密切相关。例如，研究表明，钠和氯的缺乏会降低体液免疫力，但只要摄入水平能支持最大生长，也能支持最大的体液免疫力 40。这提示动物在演化过程中，其生理对钠的需求不仅仅是为了维持基本的电解质平衡，也与免疫防御等高级生理功能紧密相连。
这些例子清晰地展示了动物在长期演化中，如何通过生理层面的精妙调整，使其自身的盐代谢与所处的自然环境和饮食结构高度匹配，从而内在地解决了对钠的需求，无需人为干预。
4. 人类与动物盐代谢的关键差异
4.1 消化与排泄系统的生理分化
人类与多数陆生动物在消化与排泄系统方面存在显著的生理分化，这些差异直接影响了它们对钠的需求和维持钠平衡的方式，尤其体现在肾脏排钠效率和汗液钠流失量上，使得人类在某些情境下更易出现钠缺乏风险。
肾脏排钠效率的差异
肾脏是调节体内钠平衡的核心器官，通过精密的过滤、重吸收和排泄机制来维持钠的稳态 41。然而，人类和许多动物在肾脏处理钠的方式上存在细微但关键的差异。
- 钠重吸收的调节：肾小管对钠的重吸收是一个复杂的调控过程，涉及多种转运蛋白和激素调节。例如，血管紧张素II和醛固酮是主要的促钠重吸收激素，它们在血容量或血压下降时被激活，促进肾脏对钠和水的保留 41。抗利尿激素（ADH，也称加压素）也通过促进远端肾单位的钠重吸收来影响水和电解质平衡 42。然而，不同物种的肾脏对这些激素的敏感性以及其下游效应器的表达水平可能存在差异。
- 肾钠排泄的长期不稳定性：经典的钠平衡理论认为，当钠摄入量增加时，总身体钠（TBNa）和水会增加，直到每日钠排泄量再次等于摄入量；反之亦然。然而，最新研究发现，总身体钠的波动可能独立于摄入量或体重而长期存在，甚至在恒定钠摄入量下，TBNa也可能表现出长期不稳定性 1543。此外，尽管肾脏能够调整钠排泄以匹配饮食摄入，但这一过程受神经内分泌机制调控，而非仅由动脉压决定 44。在生理条件下，钠的非渗透性分布（如在皮肤中储存）也是一个重要概念 15。这些复杂的调节机制可能在不同物种间存在量级和效率上的差异。
汗液钠流失量的差异
人类，特别是进行剧烈体力活动或处于炎热环境下的人类，通过汗液大量排钠是其区别于许多陆生动物的一个显著特征。
- 人类汗腺的发达：人类拥有高度发达的汗腺系统（主要是外泌腺），其主要功能是通过蒸发散热来维持体温。然而，汗液中含有显著浓度的钠离子，因此大量出汗会导致体内钠的大量流失。例如，在长时间的体育锻炼中，运动员通过汗液流失的钠量可能非常可观，从而导致低钠血症的风险增加，影响神经和肌肉功能，甚至危及生命。
- 动物汗腺的局限性：相比之下，许多陆生动物的汗腺系统不发达或功能不同。例如，狗主要通过喘息散热，马的汗腺虽然发达但其汗液成分与人类有异，许多啮齿动物和兔类几乎不通过皮肤排汗。这意味着这些动物在应对热应激时，其钠流失量远低于人类。
- 钠缺乏风险：由于人类在散热过程中不可避免地伴随着大量的钠流失，当长时间处于高强度活动、炎热环境或两者兼有的情况下，如果没有及时补充钠，人类更容易出现钠缺乏（低钠血症）的风险。这种生理特性使得人类对外部钠的补充需求更为迫切，尤其是在现代社会中，加工食品和高盐饮食的普及掩盖了人类对自然钠源的需求，但在特殊情境下，这种生理脆弱性依然存在。
综上所述，人类在肾脏排钠效率和汗液钠流失量上的生理特点，与大多数陆生动物存在显著差异。这些差异共同导致人类在特定条件下更容易面临钠缺乏的风险，从而解释了为什么人类在演化过程中逐渐发展出主动添加盐的行为，以确保钠的充足摄入。
4.2 饮食结构的根本性改变
人类与动物在盐代谢上的关键差异，除了生理分化外，饮食结构的根本性改变也是一个决定性因素。特别是自农业社会以来，人类饮食中植物性食物占比的增加以及现代加工食品的普及，对人类的盐需求产生了深远影响，这与动物长期以来遵循的自然饮食模式形成鲜明对比。
人类饮食结构的演变与钠摄入
- 植物性食物占比增加与钠含量低：农业革命使谷物和蔬菜成为人类膳食的主要组成部分。与肉类和动物产品相比，大多数植物性食物的天然钠含量通常显著偏低。例如，一份未经加工的植物性饮食，如全植物性饮食（whole-food plant-based, WFPB），通常富含钾而钠含量较低 4546。这种饮食结构导致人类从自然食物中获得的钠量不足以满足其生理需求，特别是在早期农业社会，当制盐技术尚不发达时，盐的获取可能更加困难。这种天然食物中钠与钾比例的变化，即钠钾比的失衡，被认为是现代西方饮食（Western diet）中一个重要的营养特征，与多种慢性疾病的发生有关 47。
- 加工食品的普及与人为干预：随着工业化进程和食品加工技术的发展，加工食品在人类饮食中的比重急剧上升。加工食品通常为了延长保质期、改善口感和风味而添加大量的盐，成为现代人膳食中钠的主要来源 48。例如，许多超加工食品（Ultra-Processed Foods, UPFs），如快餐、零食和预制食品，钠含量极高 4950。一项在意大利南部的研究显示，随着超加工食品消费的增加，膳食中的钠摄入量也随之增加 50。这是一种人为干预下的高钠摄入模式，与人类祖先的自然饮食截然不同，也与野生动物的饮食习惯相去甚远。
动物的自然饮食模式与钠平衡
与人类不同，大多数野生动物的饮食结构是其长期演化适应自然环境的结果，通常能够自然地满足其钠需求，而无需额外的盐添加。
- 草食动物：如前所述，草食动物通过舔食矿物盐或选择富钠植物来弥补植物性食物中钠含量低的不足。它们的饮食是未经加工的，食物中的钠含量是天然形成的。
- 肉食动物：肉食动物通过捕食猎物获取钠，因为猎物（如血液、肌肉和内脏）本身就含有充足的钠，能够满足其生理需求。这种“全食物”摄入模式，意味着它们无需担心钠的额外补充。
- 杂食动物：杂食动物的饮食更为多样，但其钠摄入通常也通过自然食物来源（植物、昆虫、小型动物等）获得，而非人为添加。
对比分析
| 特征 | 人类（农业社会后） | 动物（野生） |
|---|---|---|
| 主要钠来源 | 加工食品（人为添加盐）、烹饪时主动加盐、天然食物（少量） | 天然食物（猎物、富钠植物、矿物舔舐）、饮用水 |
| 饮食特点 | 植物性食物占比高（天然钠含量低）、加工食品普遍（高钠） | 原始、天然、未加工；钠摄入量与生物学需求匹配 |
| 钠摄入模式 | 主动寻求和添加，易出现过量摄入 | 被动获取，与生态位和生理适应性高度匹配 |
| 健康影响 | 过量钠摄入增加高血压、心血管疾病等风险 51 | 自然摄入，维持生理平衡，通常无过量或不足风险 |
这种饮食结构的根本性差异，是理解人类为何需要主动添加盐而大多数动物不需要的关键。人类的饮食从天然、低钠的原始饮食向高钠、加工的现代饮食转变，在很大程度上脱离了其基因组所适应的祖先饮食模式，从而引发了一系列健康问题，其中就包括高盐摄入带来的挑战 47。因此，人类对盐的需求不仅受到生理机制的影响，更受到饮食文化和食品工业发展的深刻塑造。
5. 特殊情境下动物的盐补充行为
5.1 极端环境与生理状态的调节
尽管多数野生动物能通过自然饮食满足盐需求，但在某些特殊情境下，如极端环境或特定的生理状态，它们也会表现出主动寻求并补充盐分的行为。这体现了动物在自然限制下，为维持生理平衡而采取的适应性策略。
迁徙动物的盐补充行为
迁徙是一个耗费巨大能量的过程，伴随着高强度的运动和大量水分流失，从而也导致电解质的消耗。为了补偿这些损失，迁徙动物可能会在迁徙路线中寻找盐分来源。例如，北美洲西部的摩门蟋蟀（Mormon crickets）在群体迁移时，会面临蛋白质和盐的严重缺乏。在这种情况下，它们甚至会表现出同类相食的行为，因为同伴的身体是这些关键营养素（包括盐）的直接来源 52。研究表明，补充蛋白质和盐可以减少同类相食现象，而充足的盐分供应也能抑制其迁徙行为 52。这表明，对盐分的强烈需求是驱动其群体迁徙和某些极端行为的内在动力之一。
哺乳期母兽的盐需求增加
哺乳期是动物生理上对营养和矿物质需求量最大的时期之一。母兽需要通过乳汁为幼崽提供生长发育所需的一切物质，其中就包括钠离子。虽然人类乳汁中钠和钾离子含量相对较低，但其他动物的乳汁成分可能有所不同 53。研究发现，在妊娠和哺乳期，大鼠对钙和钠的摄入量会增加，这可能不是由于特定的矿物质食欲或味觉敏感性改变，而是由于繁殖期整体进食量增加以满足母兽更高的矿物质和营养需求 54。例如，在亚马逊雨林中，怀孕和哺乳期的蝙蝠经常被观察到和捕获于矿物舔舐区，虽然它们访问矿物舔舐区主要可能为了缓解大量摄入植物次生化合物的毒性，而非矿物质补充，但这些舔舐区作为潜在的矿物质来源仍具有重要意义 55。
干旱地区动物的适应性策略
在干旱地区，动物不仅面临缺水问题，还可能面临盐分失衡的挑战。在这些环境中，一些动物会主动寻找含盐土壤或矿物来补充电解质。
- 舔食矿物舔舐区：矿物舔舐区（或称为盐场）是许多大型哺乳动物（如鹿、驼鹿、大象等）重要的钠来源 5657。这些区域通常富含钠、铁、铝等矿物质，尤其是在动物对钠需求较高的季节（如生长季节）访问频率更高 56。例如，生活在西伯利亚-俄罗斯边境地区的梅花鹿，在生长季节（钠需求旺盛时）对矿物舔舐区的访问显著增加，且这些舔舐区的钠含量明显高于周围环境 56。
- 对矿物质选择性：动物对矿物舔舐区的选择并非盲目。研究发现，鹿类会避开铁含量过高的舔舐区，因为过量的铁可能具有毒性 56。它们对这些含矿物质地点的选择性行为，反映了其对特定矿物质需求的精细调节。
这些案例表明，即使是那些通常被认为能通过自然饮食满足盐需求的动物，在面临特殊生理压力（如繁殖、迁徙）或极端环境（如干旱、食物资源单一）时，也会表现出高度适应性的行为，即主动寻求额外的盐分来源。这强调了盐在维持动物生存和健康中的普遍重要性，即便它们通常不需要人为干预来获取。
5.2 人工干预下的动物盐需求
虽然野生动物在自然环境中通常能够通过其演化而来的各种策略满足盐需求，但在人工干预，特别是圈养和家畜饲养的背景下，动物的饮食结构和生活方式发生了根本性变化，这往往打破了其原有的自然盐摄取平衡，使得人工补盐成为必要。
圈养动物与精饲料的影响
圈养动物，无论是农场里的家畜，还是动物园里的野生动物，其饮食通常由人类配制和提供。这种人工配制的精饲料或加工饲料，尽管在营养成分上可能力求全面，但在钠含量方面却常常难以完全模拟野生环境中的自然食物来源。
- 家畜的补盐需求：家畜（如牛、羊、猪、鸡）的饲养目的是为了提高生产性能（如生长速度、产奶量、产蛋量），因此其对营养和矿物质的需求量通常高于野生同类。精饲料往往以谷物为主，而谷物中的钠含量相对较低。例如，牛在热应激条件下，瘤胃液中的电解质（包括钠）浓度会下降，这可能进一步增加其对钠的需求 。在集约化养殖模式下，如果饲料中钠含量不足，家畜会出现生长迟缓、生产性能下降，甚至出现异食癖（如舔食尿液或泥土）等症状。因此，在畜牧业中，通过在饲料中添加食盐、提供盐砖或盐舔块，是普遍且必要的做法。对于一些特殊饲养的动物，如家猫，其商业湿粮中的钠和磷含量普遍较高，远超最低要求，有些甚至超过了国际饲料行业协会（FEDIAF）建议的安全上限 58。虽然猫粮中高钠含量有争议，但某些高钠饮食方案被用于增加猫的水摄入量和尿量，以降低尿石症风险 3259。
- 动物园动物的饮食挑战：动物园中的野生动物也面临类似的挑战。为了满足其复杂的营养需求，饲养员需要精心设计食谱。然而，要完全复制其原产地的饮食组成及其包含的微量元素（包括钠）是极其困难的。如果未能充分考虑到动物的盐需求，可能会导致矿物质缺乏。因此，动物园动物的饲料中也常会额外添加盐分或提供盐块。
与野生动物自然摄盐模式的对比
人工干预下的动物补盐行为与野生动物的自然摄盐模式形成了鲜明对比：
- 来源差异：野生动物的钠来源是天然的，如矿物舔舐区、特定植物、猎物组织或水体。这些来源在地理上分布不均，且其摄取量受动物行为和环境因素影响。而人工饲养的动物，其钠来源是人为控制的，通常是作为饲料添加剂加入或以固定形式提供。
- 摄取方式差异：野生动物会主动寻找并以舔食、啃食、捕食等方式获取钠。这种行为本身就是其适应自然环境的一部分。人工饲养的动物则通过被动摄食添加了盐的饲料，或者被动地接受盐砖。
- 适应性差异：野生动物在长期演化中形成了精密的生理适应机制（如反刍动物的唾液钠循环、海洋哺乳动物的高效排盐肾脏），使其在自然环境中无需额外补盐。而人工饲养环境下的快速饮食结构改变，使得动物的生理适应性难以跟上，从而需要人类进行干预以维持其生理平衡。例如，一项关于野猪肾脏结构的研究表明，在野外生活（面临周期性干旱或高盐饮食）的野猪，其肾脏相对髓质厚度更大，具有更好的浓缩尿液能力，以适应水盐胁迫；而人工圈养、食物和水可随意获取的野猪则相对髓质较薄，这表明肾脏结构会因环境适应而发生改变 60。
总而言之，人工干预，尤其是饲料工业的发展，虽然解决了动物基本的能量和蛋白质需求，但也带来了矿物质（尤其是钠）平衡的新挑战。在这种情况下，人工补盐成为了确保圈养动物和家畜健康与生产性能的重要手段，这与野生动物通过其精妙的自然机制获取和管理钠的方式形成了鲜明的反差。
6. 现代人类高盐饮食的健康挑战与平衡
6.1 过量盐摄入的病理风险
现代人类普遍存在高盐饮食的习惯，这主要源于烹饪时的主动加盐以及大量加工食品中隐藏的钠。然而，长期高盐摄入并非无害，它已成为全球性的公共卫生问题，与多种严重的病理风险密切相关，包括高血压、心血管疾病、肾脏负担增加以及免疫系统异常等6162。
高血压是高盐饮食最直接且广泛认可的健康后果之一。血压对膳食盐摄入量的反应称为盐敏感性高血压（SS-HT）。在盐敏感个体中，高膳食盐摄入会导致血压升高，这被认为是心血管和肾脏疾病发病率和死亡率增加的风险因素6364。尽管导致SS-HT的机制复杂，但肾脏在SS-HT的发展中起着核心作用63。高盐饮食可导致肾脏对盐负荷后的肾血流量增加反应迟钝，从而导致钠潴留和SS-HT的发生63。此外，肥胖个体对过量盐的反应，其肾素-血管紧张素-醛固酮系统（RAAS）和肾脏交感神经系统也会不恰当地激活，导致钠潴留和盐诱导的血压升高63。随着年龄的增长，SS-HT的发生率也会增加，这与肾脏钠处理能力受损和肾功能下降有关63。
心血管疾病与高血压密切相关，是高盐饮食的另一个主要病理风险。高钠饮食与多种心血管疾病（包括心力衰竭、中风和冠心病）的发生发展相关61。过量的钠摄入可能导致心脏结构和功能的改变，例如：
- 心肌机械性能改变：高钠饮食与β-肌球蛋白重链表达增加、α/β-肌球蛋白重链表达减少、肌细胞增强因子2/活化T细胞核因子转录活性增加以及盐诱导激酶1表达增加有关，这些变化可能导致心肌机械性能的改变61。
- 钙稳态和心肌收缩力异常：高钠饮食还可能影响负责钙稳态和心肌收缩力的各种蛋白质61。
- 动脉粥样硬化：高盐摄入与血管内皮功能障碍、氧化应激和炎症反应加剧有关，这些都是动脉粥样硬化发生发展的重要因素。
- 心力衰竭：高钠饮食是心力衰竭的危险因素，并可加重已有的心力衰竭症状61。尽管美国心脏病学会/美国心脏协会/美国心力衰竭协会指南建议限制钠摄入以预防和管理心力衰竭，但具体证据仍在研究中61。然而，补充天然多胺亚精胺（spermidine）能够延长小鼠寿命并具有心脏保护作用，减少心脏肥大并保留老年小鼠的舒张功能，并能降低高盐饮食喂养的大鼠的血压，延迟心力衰竭的进展65。
肾脏负担在高盐饮食中显著增加。肾脏是调节体内钠平衡的关键器官，过量的钠摄入会迫使肾脏超负荷工作，以排出多余的钠和水分，从而维持体液平衡。长期的高钠负荷可能导致：
- 肾小球高滤过：肾脏为排出多余钠，会增加肾小球的滤过压力和流量，长期可能导致肾小球损伤。
- 慢性肾脏病（CKD）进展：高钠饮食是慢性肾脏病发生和进展的风险因素之一61。钠摄入限制可以增强肾素-血管紧张素-醛固酮系统（RAAS）阻断剂在慢性肾脏病患者中的抗蛋白尿作用，降低终末期肾病和心血管不良事件的风险66。
- 肾脏损伤：盐敏感性高血压与肾脏损伤密切相关64。结合单侧肾切除术和高盐高糖高脂饮食的小鼠模型显示，这种复合因素可导致显著的肾脏损伤和功能障碍67。
免疫系统异常是近年来新兴的研究领域，揭示了高盐饮食对免疫功能的负面影响。
- TH17细胞激活：研究表明，高盐条件可以显著促进小鼠和人类致病性TH17细胞的诱导和分化686970。TH17细胞在多种自身免疫性疾病（如多发性硬化症、炎症性肠病）的发生发展中起关键作用6869。高盐饮食通过激活p38/MAPK通路，涉及活化T细胞核因子5（NFAT5）和血清/糖皮质激素调节激酶1（SGK1），促进TH17细胞的极化6870。因此，增加膳食盐摄入可能通过诱导致病性TH17细胞而成为自身免疫性疾病的环境风险因素68。
- 肠道菌群失调：高盐饮食会扰乱肠道菌群，导致有益菌（如乳杆菌科）丰度显著降低，进而影响色氨酸代谢产物5-羟吲哚乙酸（5-HIAA）的水平71。肠道菌群失调通过影响芳烃受体（AHR）/SGK1/叉头盒蛋白O1（FOXO1）轴，促进TH17细胞分化，从而加重自身免疫反应和炎症71。
- 炎症反应：高盐饮食已被证明会诱导全身性炎症67。例如，高盐饮食会通过诱导IL-17A的产生来驱动小鼠的抑郁样行为72，而IL-17A是一种由TH17细胞产生的促炎细胞因子。此外，高盐饮食还会加重慢性前列腺炎/慢性盆腔疼痛综合征（CP/CPPS），通过促进CD4 T细胞向TH17细胞分化，并涉及5-HIAA/AHR/SGK1/FOXO1轴71。
综上所述，现代人类的高盐饮食习惯，尽管在文化和历史演进中扮演了重要角色，却带来了显著的健康风险。这些风险涵盖了从宏观的循环系统到微观的免疫细胞功能，强调了控制盐摄入量对于维护人类健康的极端重要性。
6.2 合理盐摄入的科学建议
鉴于过量盐摄入带来的诸多健康风险，全球各大卫生组织和专家机构纷纷出台了合理盐摄入的科学建议，旨在引导现代人类在满足基本生理需求的同时，最大限度地降低健康风险。
全球膳食指南与钠摄入标准
世界卫生组织（WHO）是全球健康领域的领导者，其针对钠摄入量提出了明确的指导方针。WHO建议成年人每天钠摄入量不超过2克（相当于5克食盐），以预防非传染性疾病（NCDs）7374。这一推荐标准是全球各国制定本国膳食指南的重要参考依据。然而，许多国家，包括日本等亚洲国家，其历史上的高钠饮食习惯导致其推荐目标与全球标准存在差异，目前正努力通过渐进式方法与全球指南保持一致 75。尽管如此，全球饮用水标准在考虑钠相关健康风险方面普遍不足，大多数国家要么没有钠限制，要么依赖口感阈值，这些阈值对于保护健康而言过高 76。
儿童和青少年同样面临高盐饮食的挑战。研究表明，儿童和青少年摄入的钠通常超过推荐量 77。针对这一群体，特别是有肥胖风险的儿童，应制定更具体的限盐建议 77。
平衡策略：满足生理需求与避免健康风险
为了实现合理盐摄入，需要在满足生理需求和规避健康风险之间找到平衡点。核心策略包括减盐技术和饮食结构优化。
减盐技术与替代盐
- 低钠盐替代品（LSSS）：这是目前最有前景的减盐策略之一。低钠盐通常用氯化钾或其他矿物质替代部分氯化钠 78。研究表明，使用低钠盐替代普通食盐可以显著降低血压，并减少非致死性心血管事件和心血管死亡的风险 787980。例如，一项针对中国老年人群的临床试验显示，使用含62.5%氯化钠和25%氯化钾的替代盐，可使收缩压降低7.1 mmHg，并减少心血管事件的发生，且未显著增加临床高钾血症的风险 80。在血压正常的成年人中，使用替代盐也能降低高血压的发生率，而不会增加低血压的风险 81。
- 食品工业减盐策略：食品制造商在减盐方面面临挑战，因为钠不仅影响风味，还对食品的质地、保质期和微生物安全性至关重要 828384。然而，多种技术解决方案正在开发和应用，包括：
- 消费者教育：提高公众对高盐危害和减盐益处的认知至关重要 85。教育可以帮助消费者识别食品中的钠含量，并鼓励他们选择低钠食品。
饮食结构优化
尽管有研究提出低钠饮食可能存在一些健康风险，甚至一些专家认为当前关于钠与心血管疾病关联的研究缺乏完美的大规模临床试验数据 7386，但主流观点和全球指南仍强调控制钠摄入的重要性。现有的大量流行病学研究和随机对照试验已提供了足够的证据，支持通过减少钠摄入来降低高血压和心血管疾病风险的建议 787987。日本作为传统高盐饮食的国家，其通过调整膳食指南以与全球建议保持一致，也反映了对限盐重要性的认可 75。
总而言之，现代人类面对的高盐饮食挑战，需要多方面的综合策略。通过推广低钠盐替代品、实施食品工业减盐技术、加强消费者教育，并优化整体饮食结构，可以有效平衡钠的生理需求与健康风险，促进全球人群的健康福祉。
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Taku Mitome, Hiromichi Wakui, Kengo Azushima, et al.
Biochem Biophys Res Commun. 2024 Nov 19;734:150730. doi: 10.1016/j.bbrc.2024.150730. Epub 2024 Sep 28.
A regulatory mechanism for SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule, is incompletely understood. Here, we report an important regulation of SLC family transporter by SETD2, a chromatin remodeling gene whose alterations have been found in a subset of kidney cancers. Kidney-specific inactivation of Setd2 resulted in hypovolemia with excessive urine excretion in mouse and interestingly, RNA-sequencing analysis of Setd2-deficient murine kidney exhibited decreased expressions of SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule. Importantly, inactivation of Setd2 in murine kidney displayed attenuated dapagliflozin-induced diuresis and glucose excretion, further supporting that SETD2 might regulate SLCfamily transporter-mediated sodium and glucose reabsorptions in renal tubule. These data uncover an important regulation of SLC family transporter by SETD2, which may illuminate a crosstalk between metabolism and epigenome in renal tubule.
10A transmitochondrial sodium gradient controls membrane potential in mammalian mitochondria.PubMed
Pablo Hernansanz-Agustín, Carmen Morales-Vidal, Enrique Calvo, et al.
Cell. 2024 Nov 14;187(23):6599-6613.e21. doi: 10.1016/j.cell.2024.08.045. Epub 2024 Sep 19.
Eukaryotic cell function and survival rely on the use of a mitochondrial H electrochemical gradient (Δp), which is composed of an inner mitochondrial membrane (IMM) potential (ΔΨmt) and a pH gradient (ΔpH). So far, ΔΨmt has been assumed to be composed exclusively of H. Here, using a rainbow of mitochondrial and nuclear genetic models, we have discovered that a Na gradient equates with the H gradient and controls half of ΔΨmt in coupled-respiring mammalian mitochondria. This parallelism is controlled by the activity of the long-sought Na-specific Na/H exchanger (mNHE), which we have identified as the P-module of complex I (CI). Deregulation of this mNHE function, without affecting the canonical enzymatic activity or the assembly of CI, occurs in Leber's hereditary optic neuropathy (LHON), which has profound consequences in ΔΨmt and mitochondrial Ca homeostasis and explains the previously unknown molecular pathogenesis of this neurodegenerative disease.
11Central regulation of body-fluid homeostasis.PubMed
Masaharu Noda, Hiraki Sakuta
Trends Neurosci. 2013 Nov;36(11):661-73. doi: 10.1016/j.tins.2013.08.004. Epub 2013 Sep 7.
Body-fluid homeostasis is essential to life, and the concentration of Na(+) ([Na(+)]) and osmolality in plasma and the cerebrospinal fluid (CSF) are continuously monitored in the brain. To maintain a physiological level of Na/osmolality in body fluids, the control of Na and water intake and excretion are of prime importance. Two independent sensing systems for [Na(+)] and osmolality in circumventricular organs (CVOs) have long been postulated to be involved in the monitoring of body-fluid conditions. In the past decade, several molecules were reported as promising candidates for these sensors - Nax for the [Na(+)] sensor and transient receptor potential (TRP) channels for the osmosensor. This review presents a summary of developments in these areas over recent years.
12Intestinal absorptive function.PubMed
R C Spiller
Gut. 1994 Jan;35(1 Suppl):S5-9. doi: 10.1136/gut.35.1_suppl.s5.
The normal gut is adapted to intermittent feeding with complex macromolecular substrates of low sodium content. The high permeability of the upper small intestine to sodium, together with sodium rich saliva and pancreaticobiliary secretions results in large sodium fluxes into the lumen. These substantial sodium influxes are matched by equally large effluxes from the ileum and proximal colon, which are comparatively impermeable to sodium and capable of active sodium absorption. Resection of these distal, sodium absorbing regions of the intestine, lead to problems with sodium depletion. Controlled transit of chyme is essential to permit time for optimum digestion and absorption and a range of feedback control mechanisms exist. Partially digested nutrients, both in the duodenum and ileum, exert inhibitory feedback to delay delivery of further nutrients and here again surgery may compromise these reflexes. Brush border hydrolase values are strongly influenced by luminal nutrient concentrations, being impaired by malnutrition and total parenteral nutrition, but restored by enteral feeding. Viscous fibre slows absorption and may delay transit through mechanisms that are as yet uncertain. Whether and how novel substrates activate normal control mechanisms will be important factors determining their effectiveness and patient acceptability.
13Intestinal absorption following small-bowel resection.PubMed
M Perry
Ann R Coll Surg Engl. 1975 Sep;57(3):139-47.
Proximal or distal small-bowel resection was performed on female Wistar rats. Water, glucose, electrolyte, and bile acid absorption from the perfusate was studied in bile-fistula sham-operated rats and in animals 3 months after intestinal resection, using an in-vivo recirculation perfusion system. The jejunum and caecum, but not the colon, showed adaptive increases in intestinal absorption after resection of the ileum, and supranormal bile acid absorption and enhanced glucose, water, and electrolyte absorption were demonstrated in the ileum after jejunal resection. The improvement in diarrhoea observed in some patients after right hemicolectomy may be due to compensatory changes in the residual colon; rectal mucosal thickness becomes significantly increased after right hemicoletomy.
14Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability.PubMed
Andrew J King, Matthew Siegel, Ying He, et al.
Sci Transl Med. 2018 Aug 29;10(456). doi: 10.1126/scitranslmed.aam6474.
Hyperphosphatemia is common in patients with chronic kidney disease and is increasingly associated with poor clinical outcomes. Current management of hyperphosphatemia with dietary restriction and oral phosphate binders often proves inadequate. Tenapanor, a minimally absorbed, small-molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), acts locally in the gastrointestinal tract to inhibit sodium absorption. Because tenapanor also reduces intestinal phosphate absorption, it may have potential as a therapy for hyperphosphatemia. We investigated the mechanism by which tenapanor reduces gastrointestinal phosphate uptake, using in vivo studies in rodents and translational experiments on human small intestinal stem cell-derived enteroid monolayers to model ion transport physiology. We found that tenapanor produces its effect by modulating tight junctions, which increases transepithelial electrical resistance (TEER) and reduces permeability to phosphate, reducing paracellular phosphate absorption. NHE3-deficient monolayers mimicked the phosphate phenotype of tenapanor treatment, and tenapanor did not affect TEER or phosphate flux in the absence of NHE3. Tenapanor also prevents active transcellular phosphate absorption compensation by decreasing the expression of NaPi2b, the major active intestinal phosphate transporter. In healthy human volunteers, tenapanor (15 mg, given twice daily for 4 days) increased stool phosphorus and decreased urinary phosphorus excretion. We determined that tenapanor reduces intestinal phosphate absorption predominantly through reduction of passive paracellular phosphate flux, an effect mediated exclusively via on-target NHE3 inhibition.
15Mechanisms of sodium balance: total body sodium, surrogate variables, and renal sodium excretion.PubMed
Peter Bie
Am J Physiol Regul Integr Comp Physiol. 2018 Nov 1;315(5):R945-R962. doi: 10.1152/ajpregu.00363.2017. Epub 2018 Aug 15.
The classical concepts of human sodium balance include 1) a total pool of Na of ≈4,200 mmol (total body sodium, TBS) distributed primarily in the extracellular fluid (ECV) and bone, 2) intake variations of 0.03 to ≈6 mmol·kg body mass·day, 3) asymptotic transitions between steady states with a halftime (T½) of 21 h, 4) changes in TBS driven by sodium intake measuring ≈1.3 day [ΔTBS/Δ(Na intake/day)], 5) adjustment of Na excretion to match any diet thus providing metabolic steady state, and 6) regulation of TBS via controlled excretion (90-95% renal) mediated by surrogate variables. The present focus areas include 1) uneven, nonosmotic distribution of increments in TBS primarily in "skin," 2) long-term instability of TBS during constant Na intake, and 3) physiological regulation of renal Na excretion primarily by neurohumoral mechanisms dependent on ECV rather than arterial pressure. Under physiological conditions 1) the nonosmotic distribution of Na seems conceptually important, but quantitatively ill defined; 2) long-term variations in TBS represent significant deviations from steady state, but the importance is undetermined; and 3) the neurohumoral mechanisms of sodium homeostasis competing with pressure natriuresis are essential for systematic analysis of short-term and long-term regulation of TBS. Sodium homeostasis and blood pressure regulation are intimately related. Real progress is slow and will accelerate only through recognition of the present level of ignorance. Nonosmotic distribution of sodium, pressure natriuresis, and volume-mediated regulation of renal sodium excretion are essential intertwined concepts in need of clear definitions, conscious models, and future attention.
16The tubular hypothesis of nephron filtration and diabetic kidney disease.PubMed
Volker Vallon, Scott C Thomson
Nat Rev Nephrol. 2020 Jun;16(6):317-336. doi: 10.1038/s41581-020-0256-y. Epub 2020 Mar 9.
Kidney size and glomerular filtration rate (GFR) often increase with the onset of diabetes, and elevated GFR is a risk factor for the development of diabetic kidney disease. Hyperfiltration mainly occurs in response to signals passed from the tubule to the glomerulus: high levels of glucose in the glomerular filtrate drive increased reabsorption of glucose and sodium by the sodium-glucose cotransporters SGLT2 and SGLT1 in the proximal tubule. Passive reabsorption of chloride and water also increases. The overall capacity for proximal reabsorption is augmented by growth of the proximal tubule, which (alongside sodium-glucose cotransport) further limits urinary glucose loss. Hyperreabsorption of sodium and chloride induces tubuloglomerular feedback from the macula densa to increase GFR. In addition, sodium-glucose cotransport by SGLT1 on macula densa cells triggers the production of nitric oxide, which also contributes to glomerular hyperfiltration. Although hyperfiltration restores sodium and chloride excretion it imposes added physical stress on the filtration barrier and increases the oxygen demand to drive reabsorption. Tubular growth is associated with the development of a senescence-like molecular signature that sets the stage for inflammation and fibrosis. SGLT2 inhibitors attenuate the proximal reabsorption of sodium and glucose, normalize tubuloglomerular feedback signals and mitigate hyperfiltration. This tubule-centred model of diabetic kidney physiology predicts the salutary effect of SGLT2 inhibitors on hard renal outcomes, as shown in large-scale clinical trials.
17Vasopressin receptor subtypes and renal sodium transport.PubMed
Yu V Natochin, D V Golosova
Vitam Horm. 2020;113:239-258. doi: 10.1016/bs.vh.2019.08.013. Epub 2019 Oct 18.
In mammals, three subtypes of V-receptors have been identified in the kidney. The effects of vasopressin, a hormone synthesized in the hypothalamus, are triggered by three distinct receptor isoforms: V2, V1a, and V1b. Stimulation of V2-receptors regulates urine osmotic concentration by increasing sodium reabsorption in the thick ascending limb of the loop of Henle and enhancing osmotic permeability of the epithelium cells in the collecting duct. Stimulation of V1a-receptors inhibits renal sodium reabsorption and induces natriuresis, comparable to the effect of the diuretic furosemide, in the thick ascending limb of the loop of Henle. Stimulation of V1b-receptors induces potassium secretion in the final parts of the distal segments and initial parts of the collecting ducts. In this review, we discuss the role of vasopressin and its interaction with V-receptor subtypes in natriuresis and for stabilizing the physicochemical parameters of the internal environment and water-salt homeostasis in humans. A better understanding of these systems and their regulation is necessary to facilitate identification of additional system components and mechanisms, clarify their contribution during various normal and pathological functional states, and suggest novel strategies for the development of therapeutic interventions.
18Distal convoluted tubule.PubMed
Arohan R Subramanya, David H Ellison
Clin J Am Soc Nephrol. 2014 Dec 5;9(12):2147-63. doi: 10.2215/CJN.05920613. Epub 2014 May 22.
The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice.
19Regulation of distal tubule sodium transport: mechanisms and roles in homeostasis and pathophysiology.PubMed
David Pearce, Anna D Manis, Viatcheslav Nesterov, et al.
Pflugers Arch. 2022 Aug;474(8):869-884. doi: 10.1007/s00424-022-02732-5. Epub 2022 Jul 27.
Regulated Na transport in the distal nephron is of fundamental importance to fluid and electrolyte homeostasis. Further upstream, Na is the principal driver of secondary active transport of numerous organic and inorganic solutes. In the distal nephron, Na continues to play a central role in controlling the body levels and concentrations of a more select group of ions, including K, Ca, Mg, Cl, and HCO, as well as water. Also, of paramount importance are transport mechanisms aimed at controlling the total level of Na itself in the body, as well as its concentrations in intracellular and extracellular compartments. Over the last several decades, the transporters involved in moving Na in the distal nephron, and directly or indirectly coupling its movement to that of other ions have been identified, and their interrelationships brought into focus. Just as importantly, the signaling systems and their components-kinases, ubiquitin ligases, phosphatases, transcription factors, and others-have also been identified and many of their actions elucidated. This review will touch on selected aspects of ion transport regulation, and its impact on fluid and electrolyte homeostasis. A particular focus will be on emerging evidence for site-specific regulation of the epithelial sodium channel (ENaC) and its role in both Na and K homeostasis. In this context, the critical regulatory roles of aldosterone, the mineralocorticoid receptor (MR), and the kinases SGK1 and mTORC2 will be highlighted. This includes a discussion of the newly established concept that local K concentrations are involved in the reciprocal regulation of Na-Cl cotransporter (NCC) and ENaC activity to adjust renal K secretion to dietary intake.
20Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies.PubMed
Seema Patel, Abdur Rauf, Haroon Khan, et al.
Biomed Pharmacother. 2017 Oct;94:317-325. doi: 10.1016/j.biopha.2017.07.091. Epub 2017 Jul 31.
Renin-angiotensin-aldosterone system (RAAS) is a vital system of human body, as it maintains plasma sodium concentration, arterial blood pressure and extracellular volume. Kidney-secreted renin enzyme acts on its substrate to form angiotensin II, a versatile effector peptide hormone. Every organ is affected by RAAS activation and the resultant hypertension, cell proliferation, inflammation, and fibrosis. The imbalance of renin and angiotensin II can result in an overwhelming number of chronic and acute diseases. RAAS is influenced by other enzymes, hormones, pumps and signaling pathways, hence, this review discusses important facets of this system, its crosstalk with other crucial factors like estrogen, thyroid, cortisol, kallikrein-kinin system, Wnt/β-catenin signaling, and sodium-potassium pump. The nexus of RAAS with the above-discussed systems was scantily explored before. So, this review furnishes a new perspective in comprehension of inflammation diseases. It is followed by the formulation of hypotheses, which can contribute to better management of an array of pathologies plaguing mankind. Manipulation of RAAS, by bending it towards ACE2 expression can regulate endocrine functions, which can be critical for a number of pathological management. Dietary intervention can restore RAAS to normalcy.
21Thirst and hydration: physiology and consequences of dysfunction.PubMed
Simon N Thornton
Physiol Behav. 2010 Apr 26;100(1):15-21. doi: 10.1016/j.physbeh.2010.02.026. Epub 2010 Mar 6.
The constant supply of oxygen and nutriments to cells (especially neurons) is the role of the cardiovascular system. The constant supply of water (and sodium) for cardiovascular function is the role of thirst and sodium appetite and kidney function. This physiological regulation ensures that plasma volume and osmolality are maintained within set limits by initiating behaviour and release of hormones necessary to ingest and conserve water and sodium within the body. This regulation is separated into 2 parts; intracellular and extracellular (blood). An increased osmolality draws water from cells into the blood thus dehydrating specific brain osmoreceptors that stimulate drinking and release of anti diuretic hormone (ADH or vasopressin). ADH reduces water loss via lowered urine volume. Extracellular dehydration (hypovolaemia) stimulates specific vascular receptors that signal brain centres to initiate drinking and ADH release. Baro/volume receptors in the kidney participate in stimulating the release of the enzyme renin that starts a cascade of events to produce angiotensin II (AngII), which initiates also drinking and ADH release. This stimulates also aldosterone release which reduces kidney loss of urine sodium. Both AngII and ADH are vasoactive hormones that could work to reduce blood vessel diameter around the remaining blood. All these events work in concert so that the cardiovascular system can maintain a constant perfusion pressure, especially to the brain. Even if drinking does not take place ADH, AngII and aldosterone are still released. Furthermore, it has been observed that treatment of hypertension, obesity, diabetes and cancer can involve renin-AngII antagonists which could suggest that, in humans at least, there may be dysfunction of the thirst regulatory mechanism.
22Tangram of Sodium and Fluid Balance.PubMed
Domenico Bagordo, Gian Paolo Rossi, Christian Delles, et al.
Hypertension. 2024 Mar;81(3):490-500. doi: 10.1161/HYPERTENSIONAHA.123.19569. Epub 2023 Dec 12.
Homeostasis of fluid and electrolytes is a tightly controlled physiological process. Failure of this process is a hallmark of hypertension, chronic kidney disease, heart failure, and other acute and chronic diseases. While the kidney remains the major player in the control of whole-body fluid and electrolyte homeostasis, recent discoveries point toward more peripheral mechanisms leading to sodium storage in tissues, such as skin and muscle, and a link between this sodium and a range of diseases, including the conditions above. In this review, we describe multiple facets of sodium and fluid balance from traditional concepts to novel discoveries. We examine the differences between acute disruption of sodium balance and the longer term adaptation in chronic disease, highlighting areas that cannot be explained by a kidney-centric model alone. The theoretical and methodological challenges of more recently proposed models are discussed. We acknowledge the different roles of extracellular and intracellular spaces and propose an integrated model that maintains fluid and electrolyte homeostasis and can be distilled into a few elemental players: the microvasculature, the interstitium, and tissue cells. Understanding their interplay will guide a more precise treatment of conditions characterized by sodium excess, for which primary aldosteronism is presented as a prototype.
23Salt and water: not so simple.PubMed
Mark L Zeidel
J Clin Invest. 2017 May 1;127(5):1625-1626. doi: 10.1172/JCI94004. Epub 2017 Apr 17.
It has long been viewed that the maintenance of osmotic balance in response to high salt intake is a passive process that is mediated largely by increased water consumption to balance the salt load. Two studies in this issue of the JCI challenge this notion and demonstrate that osmotic balance in response to high salt intake involves a complex regulatory process that is influenced by hormone fluctuation, metabolism, food consumption, water intake, and renal salt and water excretion. Rakova et al. report the unexpected observation that long-term high salt intake did not increase water consumption in humans but instead increased water retention. Moreover, salt and water balance was influenced by glucocorticoid and mineralocorticoid fluctuations. Kitada et al. extend upon these findings in mouse models and determined that increased urea and a corresponding increase in urea transporters in the renal medulla as the result of increased protein intake promote the water retention that is needed to achieve osmotic homeostasis. Together, the results of these two studies lay the groundwork for future studies to determine how, in the face of chronic changes in salt intake, humans maintain volume and osmotic homeostasis.
24Sodium, hypertension, and an explanation of the "lag phenomenon" in hemodialysis patients.PubMed
Zbylut J Twardowski
Hemodial Int. 2008 Oct;12(4):412-25. doi: 10.1111/j.1542-4758.2008.00304.x.
Sodium balance is precisely regulated by intake and output. The kidneys are responsible for adjusting sodium excretion to maintain balance at varying intakes. Our distant ancestors were herbivores. Their diet contained little sodium, so they developed powerful mechanisms for conserving sodium and achieving low urinary excretion. About 10,000 years ago, early humans became villagers and discovered that food could be preserved in brine. This led to increased consumption of salt. High salt intake increases extracellular volume (ECV), blood volume, and cardiac output resulting in elevation of blood pressure. High ECV induces release of a digitalis-like immunoreactive substance and other inhibitors of Na(+)-K(+)-ATPase. As a consequence, intracellular sodium and calcium concentrations increase in vascular smooth muscles predisposing them to contraction. Moreover, high ECV increases synthesis and decreases clearance of asymmetrical dimethyl-l-arginine leading to inhibition of nitric oxide (NO) synthase. High concentration of sodium and calcium in vascular smooth muscles, and decreased synthesis of NO lead to an increase in total peripheral resistance. Restoration of normal ECV and blood pressure are attained by increased glomerular filtration and decreased sodium reabsorption. In some individuals, the kidneys have difficulty in excreting sodium, so the equilibrium is achieved at the expense of elevated blood pressure. There is some lag time between reduction of ECV and normalization of blood pressure because the normal levels of Na(+)-K(+)-ATPase inhibitors and asymmetrical dimethyl-l-arginine are restored slowly. In dialysis patients, all mechanisms intended to increase renal sodium removal are futile but they still operate and elevate blood pressure. The sodium balance must be achieved via dialysis and ultrafiltration. Blood pressure is normalized a few weeks after ECV is returned to normal, i.e., when the patient reaches dry body weight. This is called the "lag phenomenon."
25Preserving the food preservation legacy.PubMed
Dietrich Knorr, Mary Ann Augustin
Crit Rev Food Sci Nutr. 2023;63(28):9519-9538. doi: 10.1080/10408398.2022.2065459. Epub 2022 Apr 20.
This paper deals with the question about how early humans managed to feed themselves, and how they preserved and stored food for times of need. It attempts to show how humans interacted with their environments and demonstrate what lessons can be learnt from the about 3.4 million years of food processing and preservation. It includes a discussion about how hominins shifted from consumption of nuts and berries toward meat and learnt to control and use fire. Cooking with fire generated more food-related energy and enabled humans to have more mobility. The main trust of the paper is on historical food preservations, organized from the perspectives of key mechanical, thermal, biological and chemical processes. Emerging food processes are also highlighted. Furthermore, how humans historically dealt with food storage and packaging and how early humans interacted with their given environments are discussed. Learnings from the history of food preservation and culinary practices of our ancestors provide us with an understanding of their culture and how they adapted and lived with their given environments to ensure adequacy of food supply. Collaboration between food scientists and anthropologists is advocated as this adds another dimension to building resilient and sustainable food systems for the future.
26Brain evolution, the determinates of food choice, and the omnivore's dilemma.PubMed
George J Armelagos
Crit Rev Food Sci Nutr. 2014;54(10):1330-41. doi: 10.1080/10408398.2011.635817.
A coevolutionary paradigm using a biocultural perspective can help to unravel the complex interactions that led to the contemporary pattern of eating. Evolutionary history helps to understand the adaptation of diet and its nutritional implications. Anatomical and behavioral changes linked to changing dietary patterns in the Paleolithic resulted in an adaptive framework that affects modern diet. The evolution of an expanding brain, a shrinking large intestine, and lengthening small intestine necessitated a demand for nutritionally dense foods. The key to these changes is an understanding of the response to the omnivore's dilemma. Omnivores in their search for new items to feed their varied diet (neophilia) have a challenge when they fear (neophobia) novel items that may be poisonous and can cause death. The inborn mechanism initiates palate fatigue (sensory-specific satiety) ensuring a variety of foods will be eaten. Variety will limit the impact of toxins ingested and provide a more balanced diet. The development of cuisine, a momentous event in history, mediated the conflict, and changed the course of human evolution. The cuisine, a biocultural construct, defines which items found in nature are edible, how these products are transformed into food, the flavors used to add a sensory dimension to foods, and rules of eating or etiquette. Etiquette defines how, when, and with whom we eat. Patterns of eating in the modern setting are the end product of the way that Homo sapiens evolved and resolved the omnivore's dilemma. Control of fire and cooking expanded the range of available foods by creating a class of foods that are "predigested." An essential element to the evolution of the human diet was the transition to agriculture as the primary mode of subsistence. The Neolithic revolution dramatically narrowed the dietary niche by decreasing the variety of available foods, with the shift to intensive agriculture creating a dramatic decline in human nutrition. The recent industrialization of the world food system has resulted in a nutritional transition in which developing nations are simultaneously experiencing undernutrition and obesity. In addition, an abundance of inexpensive, high-density foods laden with sugar and fats is available to a population that expends little energy to obtain such large numbers of calories. Furthermore, the abundant variety of ultraprocessed foods overrides the sensory-specific satiety mechanism leading to overconsumption.
27Influence of Cooking Method on the Nutritional Quality of Organic and Conventional Brazilian Vegetables: A Study on Sodium, Potassium, and Carotenoids.PubMed
Neide Torres de Castro, Ernandes Rodrigues de Alencar, Renata Puppin Zandonadi, et al.
Foods. 2021 Jul 31;10(8):1782. doi: 10.3390/foods10081782.
Vegetable consumption is associated with increased health benefits, and vegetables are consumed both in cooked form and raw form in salads. All cooking techniques cause changes in a vegetable's the nutrient content. Consumers are increasingly health-conscious and have less time to prepare meals, and they do not know which cooking times and cooking methods are best suited to preserve the nutrients. This study aimed to determine the best method of cooking vegetables to maintain minerals (potassium and sodium) and carotenoids. The studied vegetables were broccoli (, var. Italica), carrots (), and zucchini (). The cooking methods were: boiling, steaming, combined oven, microwave steaming, and microwave cooking. Samples of organic and conventionally grown vegetables were prepared in triplicate. Samples were analyzed to determine the availability of target minerals and carotenoids in the raw food and in each recommended cooking situation according to technical standards. Only the carrot showed a higher concentration in organic cultivation for carotenoids in raw vegetables, with both zucchini and broccoli having higher concentrations when grown by conventional cultivation. The zucchini from organic cultivation presented a reduction of potassium and sodium, almost consistently, in all cooking techniques. Regarding the conventionally cultivated zucchini, potassium remained stable in boiling. Broccoli from organic and conventional cultivation showed similar potassium levels for boiling and traditional steam cooking. Organic carrots showed easier sodium extraction compared with conventional cultivation. Heat treatment, in general, improves the accessibility of carotenoids.
28Novel strategies for controlling nitrite content in prepared dishes: Current status, potential benefits, limitations and future challenges.PubMed
Tiantian Tang, Min Zhang, Chung Lim Law, et al.
Food Res Int. 2023 Aug;170:112984. doi: 10.1016/j.foodres.2023.112984. Epub 2023 May 18.
Sodium nitrite is commonly used as a multifunctional curing ingredient in the processing of prepared dishes, especially meat products, to impart unique color, flavor and to prolong the shelf life of such products. However, the use of sodium nitrite in the meat industry has been controversial due to potential health risks. Finding suitable substitutes for sodium nitrite and controlling nitrite residue have been a major challenge faced by the meat processing industry. This paper summarizes possible factors affecting the variation of nitrite content in the processing of prepared dishes. New strategies for controlling nitrite residues in meat dishes, including natural pre-converted nitrite, plant extracts, irradiation, non-thermal plasma and high hydrostatic pressure (HHP), are discussed in detail. The advantages and limitations of these strategies are also summarized. Raw materials, cooking techniques, packaging methods, and storage conditions all affect the content of nitrite in the prepared dishes. The use of vegetable pre-conversion nitrite and the addition of plant extracts can help reduce nitrite residues in meat products and meet the consumer demand for clean labeled meat products. Atmospheric pressure plasma, as a non-thermal pasteurization and curing process, is a promising meat processing technology. HHP has good bactericidal effect and is suitable for hurdle technology to limit the amount of sodium nitrite added. This review is intended to provide insights for the control of nitrite in the modern production of prepared dishes.
29Salt and marine products in the Classic Maya economy from use-wear study of stone tools.PubMed
Heather McKillop, Kazuo Aoyama
Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):10948-10952. doi: 10.1073/pnas.1803639115. Epub 2018 Oct 8.
Microscopic study of the edges of Late to Terminal Classic Maya (AD 600-900) chert stone tools from the Paynes Creek Salt Works, Belize, indicates most tools were used for cutting fish or meat or working hide, which was unexpected, given the virtual absence of fish or other animal remains at this large salt-production complex. Use-wear study shows that a minority of stone tools have edge-wear from woodworking. Our study suggests that salting fish was a significant activity at the salt works, which corresponds to Roman, Chinese, and other East Asian civilizations, where salt and salted fish were critical components of food storage, trade, and state finance. Based on analogy with modern Maya salt producers at Sacapulas, Guatemala, we provide estimates of the amounts of salt and salted fish produced at the Paynes Creek Salt Works and the implications for the Classic Maya economy. Salt cakes and salted fish were preserved commodities that could be stored and traded in the marketplace.
30The seventh macronutrient: how sodium shortfall ramifies through populations, food webs and ecosystems.PubMed
Michael Kaspari
Ecol Lett. 2020 Jul;23(7):1153-1168. doi: 10.1111/ele.13517. Epub 2020 May 7.
Of the 25 elements required to build most organisms, sodium has a unique set of characteristics that ramify through terrestrial ecology. In plants, sodium is found in low concentrations and has little metabolic function; in plant consumers, particularly animals, sodium is essential to running costly Na-K ATPases. Here I synthesise a diverse literature from physiology, agronomy and ecology, towards identifying sodium's place as the '7th macronutrient', one whose shortfall targets two trophic levels - herbivores and detritivores. I propose that sodium also plays a central, though unheralded role in herbivore digestion, via its importance to maintaining microbiomes and denaturing tannins. I highlight how sodium availability is a key determinant of consumer abundance and the geography of herbivory and detritivory. And I propose a re-appraisal of the assumption that, because sodium is metabolically unimportant to most plants, it is of little use. Instead, I suggest that sodium's critical role in limiting herbivore performance makes it a commodity used by plants to manipulate their herbivores and mutualists, and by consumers like bison and elephants to generate grazing lawns: dependable sources of sodium.
31Geophagy in animals and geology of kudurs (mineral licks): a review of Russian publications.PubMed
A M Panichev, K S Golokhvast, A N Gulkov, et al.
Environ Geochem Health. 2013 Feb;35(1):133-52. doi: 10.1007/s10653-012-9464-0. Epub 2012 Jun 15.
This paper reviews from the geological and biological perspectives the achievements of Russian researchers in the field of geophagy, which have not been published in English. It is focused on publications in Russian language about (1) animal behavior related to geophagy, (2) mineral and chemical composition as well as geological characteristics and biological effects of the earths, eaten by animals in various locations in Russia and neighboring countries. The authors argue that the Russian term "solonetz" (salt lick) is too limiting, as animals consume not just salt but many other minerals too. The more general term "kudur" is used for places where animals eat earths. The geological nature and biological properties of kudurites (the common name given to biologically active mineral-crystal substances consumed by animals) and gastroliths (stones consumed by birds and reptiles) are addressed. On the basis of the reviewed data, the authors propose their own views regarding the causes of geophagy.
32Sodium in feline nutrition.PubMed
P Nguyen, B Reynolds, J Zentek, et al.
J Anim Physiol Anim Nutr (Berl). 2017 Jun;101(3):403-420. doi: 10.1111/jpn.12548. Epub 2016 Aug 23.
High sodium levels in cat food have been controversial for a long time. Nonetheless, high sodium levels are used to enhance water intake and urine volume, with the main objective of reducing the risk of urolithiasis. This article is a review of current evidence of the putative risks and benefits of high dietary sodium levels. Its secondary aim is to report a possible safe upper limit (SUL) for sodium intake. The first part of the manuscript is dedicated to sodium physiology, with a focus on the mechanisms of sodium homeostasis. In this respect, there is only few information regarding possible interactions with other minerals. Next, the authors address how sodium intake affects sodium balance; knowledge of these effects is critical to establish recommendations for sodium feed content. The authors then review the consequences of changes in sodium intake on feline health, including urolithiasis, blood pressure changes, cardiovascular alterations and kidney disease. According to recent, long-term studies, there is no evidence of any deleterious effect of dietary sodium levels as high as 740 mg/MJ metabolizable energy, which can therefore be considered the SUL based on current knowledge.
33Pet food safety: sodium in pet foods.PubMed
Marjorie L Chandler
Top Companion Anim Med. 2008 Aug;23(3):148-53. doi: 10.1053/j.tcam.2008.04.008.
Healthy dogs and cats appear to be able to adjust to differing amounts of sodium in their diet via the rennin-angiotensin-aldosterone mechanisms. There is no strong evidence that increased dietary sodium increases the risk of hypertension in dogs and cats, and the current recommendation for hypertensive animals is to avoid high dietary salt intake without making a specific effort to restrict it. The prevalence of salt sensitivity and its effect on blood pressure has not been determined for cats or dogs. The ideal amount of sodium in the diet of dogs and cats with cardiac deficiency has not been determined, as increasing may detrimentally increase the extracellular fluid volume, but decreasing it may detrimentally increase the activation of the rennin-angiotensin-aldosterone system. Increased dietary sodium increases urine output and may decrease the risk of forming calcium oxalate uroliths due to the decrease in relative supersaturation of solutes. However, caution should be used in increasing the sodium intake of patients with renal disease as increased dietary sodium may have a negative effect on the kidneys independent of any effect on blood pressure.
34Antagonistic bioaccumulation of waterborne Cu(II) and Cd(II) in common carp (Cyprinus carpio) and effects on ion-homeostasis and defensive mechanisms.PubMed
G Castaldo, G Flipkens, M Pillet, et al.
Aquat Toxicol. 2020 Sep;226:105561. doi: 10.1016/j.aquatox.2020.105561. Epub 2020 Jul 3.
In the aquatic environment, metals are present as mixtures, therefore studies on mixture toxicity are crucial to thoroughly understand their toxic effects on aquatic organisms. Common carp (Cyprinus carpio) were used to assess the effects of short-term Cu(II) and Cd(II) mixtures, using a fixed concentration of one of the metals, representing 25 % of its individual 96h-LC (concentration lethal for 50 % of the population) combined with a variable concentration of the other metal corresponding to 10, 25 or 50 % of its 96h-LC, and vice versa. Our results showed a fast Cu and Cd bioaccumulation, with the percentage of increase in the order gill > liver > carcass. An inhibitory effect of Cu on Cd uptake was observed; higher Cu concentrations at fixed Cd levels resulted in a decreased accumulation of Cd. The presence of the two metal ions resulted in losses of total Na, K and Ca. Fish tried to compensate for the Na loss through the induction of the genes coding for Na/K-ATPase and H-ATPase. Additionally, a counterintuitive induction of the gene encoding the high affinity copper transporter (CTR1) occurred, while a downregulation was expected to prevent further metal ion uptake. An induction of defensive mechanisms, both metal ion binding protein and anti-oxidant defences, was observed. Despite the metal accumulation and electrolyte loss, the low mortality suggest that common carp is able to cope with these metal levels, at least during a one-week exposure.
35Postnatal development of salivary phosphate, sodium and potassium secretion in calves.PubMed
Alexandra S Muscher-Banse, Reinhard Daenicke, Sven Dänicke, et al.
Front Vet Sci. 2023 Dec 19;10:1294899. doi: 10.3389/fvets.2023.1294899. eCollection 2023.
The transition of young lambs and calves from a non-ruminating to a ruminating animal include substantial, developmental changes to alter saliva production. Due to the simultaneous development of the forestomach system, the salivary glands must transfer more and more substances such as bicarbonate and phosphate (Pi), but also sodium (Na), into saliva in order to create and to maintain optimal environmental conditions for microbial metabolism. The objective of the present study was to characterize the effects of different dietary energy levels on the ability of the salivary glands to concentrate minerals in young ruminants in more detail during the first 7 weeks of life. Blood and saliva samples were collected from twelve female calves of the German Holstein breed fed different levels of milk replacer. Plasma and saliva samples were collected over 7 weeks postpartum and Na, Pi and potassium (K) concentrations were measured. Salivary Na and Pi concentrations ( < 0.001) increased as a function of time and were not affected by varying energy intake, while K concentration ( < 0.001) decreased over the developmental period and was also not affected by energy intake. This suggests that the ability to specifically concentrate minerals such as Na and Pi in saliva follows a genetic program in the salivary glands rather than being influenced by dietary factors such as energy intake in young ruminants.
36The struggle to maintain hydration and osmoregulation in animals experiencing severe dehydration and rapid rehydration: the story of ruminants.PubMed
N Silanikove
Exp Physiol. 1994 May;79(3):281-300. doi: 10.1113/expphysiol.1994.sp003764.
Ruminants in tropical and desert areas routinely experience cycles of severe dehydration and rapid rehydration. These animals can withstand severe dehydration (18-40% of initial body weight), which exceeds considerably the capacity of most monogastric mammals. This capacity is related to their ability to use, during the course of dehydration, their large water reservoir in the rumen, which contributes 50-70% of the total water loss. As rumen fluid is in approximate isotonicity with systemic fluid, the utilization of gut water during the course of dehydration involves a considerable load of sodium and potassium. Consequently, the effectiveness of utilization of rumen fluid during dehydration depends on the capacity of the kidney to 'desalt' the water absorbed from the gut and on maintenance of salivary flow to the rumen. Following rehydration, ruminants can imbibe their entire water deficit in one drinking and the entire amount ingested is first retained in the rumen. The rumen volume at this stage may exceed the extracellular fluid volume and the sudden drop in rumen osmolality creates a huge osmotic gradient (200-300 mosmol kg-1) between the rumen and systemic fluid. Ruminant animals are confronted at this stage by two opposing tasks, each of them of vital importance: (i) the need to prevent the osmotic hazard leading to water intoxication; and (ii) the need to retain the ingested water, so that it is not missing for the next dehydration cycle. The most prevalent view until recently was a theory which attributes an osmotic protective mechanism to the rumen wall. However, such a capacity has not yet been demonstrated and is challenged by contradictory observations that large amounts of water are absorbed from the rumen following rehydration. The view that is most consistent with available information is that gustatory-alimentary and hepatoportal signals regarding the presence of large amounts of water in the rumen and the absorption of water from the gut activate a range of homeostatic responses involved in fluid and sodium restitution. The efferent elements, presumably activated by the CNS, include: a dramatic increase in secretion of hypotonic saliva and, reciprocally, a dramatic drop in urine flow. The enhanced saliva secretion recycles a considerable portion of the water absorbed from the gut back to the rumen, which allows effective retention of water while avoiding the danger of osmotic threat to the red blood cells. The enhanced saliva secretion also drains large amounts of sodium and bicarbonate from the blood. Accompanying responses are marked retention of sodium and carbonic acid in the kidney.(ABSTRACT TRUNCATED AT 400 WORDS)
37Influences of environment and its modification on dairy animal health and production.PubMed
R J Collier, D K Beede, W W Thatcher, et al.
J Dairy Sci. 1982 Nov;65(11):2213-27. doi: 10.3168/jds.S0022-0302(82)82484-3.
Physiological state of dairy animals is a predisposing factor in environmental influences on animal health. Critical phases of life cycle include neonatal period, postpubertal reproduction, and lactation. Primary effect of environment in neonatal period is increased disease incidence associated with reduced immunoglobulin content in plasma of calves. Cold stress has little effect on reproduction; in contrast, heat stress reduces libido, fertility, and embryonic survival in cattle. Heat stress in late gestation reduces fetal growth and alters endocrine status of the dam. Carryover effects of heat stress during late gestation on postpartum lactation and reproduction also are detectable. Heat stress of lactating cattle results in dramatic reductions in roughage intake and rumination. Decreases in roughage intake contribute to decreased volatile fatty acid production and may contribute to alteration in ratio of acetate/propionate. Rumen pH also declines during thermal stress. Electrolyte concentrations, in particular sodium and potassium, also are reduced in rumen fluid of heat stressed cattle. The decrease in sodium and potassium are related to increases in loss of urinary sodium and loss of skin potassium as well as decline in plasma aldosterone and increase in plasma prolactin. Reduction in thyroxine, growth hormone, and glucocorticoid concentrations in chronically heat stressed cattle appear to be related to decreases in basal metabolism.
38Osmoregulation in marine mammals.PubMed
R M Ortiz
J Exp Biol. 2001 Jun;204(Pt 11):1831-44. doi: 10.1242/jeb.204.11.1831.
Osmoregulation in marine mammals has been investigated for over a century; however, a review of recent advances in our understanding of water and electrolyte balance and of renal function in marine mammals is warranted. The following topics are discussed: (i) kidney structure and urine concentrating ability, (ii) sources of water, (iii) the effects of feeding, fasting and diving, (iv) the renal responses to infusions of varying salinity and (v) hormonal regulation. The kidneys of pinnipeds and cetaceans are reniculate in structure, unlike those of terrestrial mammals (except bears), but this difference does not confer any greater concentrating ability. Pinnipeds, cetaceans, manatees and sea otters can concentrate their urine above the concentration of sea water, but only pinnipeds and otters have been shown to produce urine concentrations of Na+ and Cl- that are similar to those in sea water. This could afford them the capacity to drink sea water and not lose fresh water. However, with few exceptions, drinking is not a common behavior in pinnipeds and cetaceans. Water balance is maintained in these animals via metabolic and dietary water, while incidental ingestion and dietary salt may help maintain electrolyte homeostasis. Unlike most other aquatic mammals, sea otters commonly drink sea water and manatees frequently drink fresh water. Among the various taxonomic groups of marine mammals, the sensitivity of the renin-angiotensin-aldosterone system appears to be influenced by the availability of Na+. The antidiuretic role of vasopressin remains inconclusive in marine mammals, while the natriuretic function of atrial natriuretic peptide has yet to be examined. Ideas on the direction of future studies are presented.
39Effects of freshwater housing and fluid types on aquatic bird serum electrolyte concentrations.PubMed
Greg Frankfurter, Michael H Ziccardi, J Gregory Massey
J Zoo Wildl Med. 2012 Dec;43(4):852-7. doi: 10.1638/2012-0076R.1.
Recent seabird mass morbidity events have highlighted the need to elucidate the effects of freshwater and hypertonic saline use for fluid therapy and housing in captive aquatic birds. Serum electrolyte concentrations of northern fulmars (Fulmarus glacialis; n = 9), western grebes (Aechmophorus occidentalis; n = 6), and common murres (Uria aalge; n = 25) housed on freshwater while undergoing rehabilitation at the San Francisco Bay Oiled Wildlife Care and Education Center in Fairfield, California, were compared to reference intervals from free-ranging populations. Additionally, northern fulmars were given intermittent oral boluses of hypertonic saline. In birds housed on freshwater, there were significant decreases in serum sodium and chloride, with 44% of northern fulmars and 72% of common murres falling below the established reference interval. All of the western grebes were able to maintain serum sodium and chloride within the reference intervals. The significance of these findings reflect the behavior and natural history of the species studied. The physiologic regulation of salt by the salt glands, gastrointestinal tract, and renal systems of seabirds, along with their behavior and natural history, should be considered when working with these birds in a rehabilitation or captive setting. Salt supplementation is necessary for some species of seabirds. Monitoring of serum electrolytes should be used for individual animals or salt supplementation should be considered in holopelagic species.
40Nutrition--mechanisms of immunosuppression.PubMed
J D Latshaw
Vet Immunol Immunopathol. 1991 Nov;30(1):111-20. doi: 10.1016/0165-2427(91)90012-2.
Nutritionists must formulate diets that supply adequate amounts of nutrients from five major groups. These are carbohydrate, protein (amino acids), fat, minerals and vitamins. Carbohydrate is usually a cheaper source of energy than fat, but fat is often used to increase the caloric concentration of the diet. Variations in energy intake which may effect immunocompetence usually result from management practices rather than diet formulation. Feed restriction for broiler breeders and withholding feed in forced molting practices may affect immunocompetence. Feed restriction causes higher plasma corticosterone levels, which are known to decrease the immune response, possibly through effects on cytokines. Excessive feed, through forced feeding, may also have short-term effects on indicators of humoral immunity. Protein and amino acid nutrition have been studied in relation to immunocompetence. The level of dietary amino acid needed to maximize growth and feed efficiency will also generally maximize measures of immunocompetence. The level of amino acids needed for maximum growth is lower in chicks which have been immunologically stressed than in chicks which have not. An immune response changes metabolism so that less growth occurs, thereby decreasing the need for amino acids. Dietary levels of minerals can affect immunocompetence. While deficient levels of sodium and chloride decrease humoral immunity, levels of these nutrients which supported maximum growth also supported maximal humoral immunity. Low dietary zinc levels did not affect indicators of immunocompetence in the chick. The effect of fat soluble vitamin levels on the immune system has been studied. Vitamin A is needed to maintain epithelial tissue and prevent infection. Cellular immune response is decreased when the chick is deficient in this nutrient. Several indicators of immune responsiveness are depressed when chicks are vitamin E and/or selenium deficient. Since these nutrients serve as antioxidants, cellular integrity may be affected by a deficiency. Cellular integrity is very important for receiving, and responding to the messages needed to coordinate an immune response. High levels of vitamin E (greater than 10 times the required level) have been found to be immunostimulatory.
41[Sodium homeostasis].PubMed
P Houillier
Nephrol Ther. 2007 Sep;3 Suppl 2:S91-3. doi: 10.1016/s1769-7255(07)80014-9.
Sodium content in the body is maintained within narrow limits, despite large variations in dietary sodium intake. The reason is that renal tubular sodium reabsorption and, therefore, sodium excretion can rapidly adapt thanks to endo-, para- and autocrine factors. The near constancy of sodium content guarantees the maintenance of plasma volume and blood pressure in the normal range.
42Vasopressin regulation of renal sodium excretion.PubMed
James D Stockand
Kidney Int. 2010 Nov;78(9):849-56. doi: 10.1038/ki.2010.276. Epub 2010 Aug 25.
Vasopressin promotes renal water reabsorption decreasing excretion of free water to dilute plasma and lower serum osmolality. We have good understanding of the causes, mechanisms and consequences of this vasopressin-dependent renal water movement. In comparison, vasopressin actions on renal electrolytes including sodium excretion and its consequences have been less well understood. This is so for investigation and discussions of the renal actions of vasopressin are framed primarily around water metabolism rather than any direct effect on salt handling. The fact that water moves in biological systems, to include the mammalian kidney, only by osmosis passively down its concentration gradient is implicit in such discussion but often not overtly addressed. This can cause confusion. Moreover, although vasopressin action on renal sodium excretion via the V2 receptor is critical to water transport, it is masked easily being situational--for instance, dependent on hydration state. It is now clear that an increase in sodium reabsorption along the distal nephron (CNT + CD) mediated by activation of the epithelial Na(+) channel (ENaC) by vasopressin makes an important contribution to maintenance of the axial corticomedullary osmotic gradient necessary for maximal water reabsorption. Thus, we need to modify slightly our understanding of vasopressin and its renal actions to include the idea that while vasopressin decreases free water excretion to dilute plasma, it does this, in part, by promoting sodium reabsorption and consequently decreasing sodium excretion via ENaC activated along the distal nephron.
43Spooky sodium balance.PubMed
Jens Titze, Anke Dahlmann, Kathrin Lerchl, et al.
Kidney Int. 2014 Apr;85(4):759-67. doi: 10.1038/ki.2013.367. Epub 2013 Oct 9.
Current teaching states that when sodium intake is increased from low to high levels, total-body sodium (TBNa) and water increase until daily sodium excretion again equals intake. When sodium intake is reduced, sodium excretion briefly exceeds intake until the excess TBNa and water are eliminated, at which point sodium excretion again equals intake. However, careful balance studies oftentimes conflict with this view and long-term studies suggest that TBNa fluctuates independent of intake or body weight. We recently performed the opposite experiment in that we fixed sodium intake for several weeks at three levels of sodium intake and collected all urine made. We found weekly (circaseptan) patterns in sodium excretion that were inversely related to aldosterone and directly to cortisol. TBNa was not dependent on sodium intake but instead exhibited far longer (≥ monthly) infradian rhythms independent of extracellular water, body weight, or blood pressure. The findings are consistent with our ideas on tissue sodium storage and its regulation that we developed on the basis of animal research. We are implementing (23)Na-magnetic resonance imaging (MRI) to pursue open questions on sodium balance in patients. Our findings could be relevant to therapeutic strategies for hypertension and target-organ damage.
44Volume natriuresis vs. pressure natriuresis.PubMed
P Bie, S Wamberg, M Kjolby
Acta Physiol Scand. 2004 Aug;181(4):495-503. doi: 10.1111/j.1365-201X.2004.01323.x.
Body fluid regulation depends on regulation of renal excretion. This includes a fast vasopressin-mediated water-retaining mechanism, and slower, complex sodium-retaining systems dominated by the renin-angiotensin aldosterone cascade. The sensory mechanisms of sodium control are not identified; effectors may include renal arterial pressure, renal reflexes, extrarenal hormones and other regulatory factors. Since the pioneering work of Guyton more than three decades ago, pressure natriuresis has been in focus. Dissociations between sodium excretion and blood pressure are explained as conditions where regulatory performance exceeds the precision of the measurements. It is inherent to the concept, however, that sudden transition from low to high sodium intake elicits an arterial pressure increase, which is reversed by the pressure natriuresis mechanism. However, such transitions elicit parallel changes in extracellular fluid volume thereby activating volume receptors. Recently we studied the orchestration of sodium homeostasis by chronic and acute sodium loading in normal humans and trained dogs. Small increases in arterial blood pressure are easily generated by acute sodium loading, and dogs appear more sensitive than humans. However, with suitable loading procedures it is possible - also acutely - to augment renal sodium excretion by at least one order of magnitude without any change in arterial pressure whatsoever. Although pressure natriuresis is a powerful mechanism capable of overriding any other controller, it seems possible that it is not operative under normal conditions. Consequently, it is suggested that physiological control of sodium excretion is neurohumoral based on extracellular volume with neural control of renin system activity as an essential component.
45Low dietary sodium potentially mediates COVID-19 prevention associated with whole-food plant-based diets.PubMed
Ronald B Brown
Br J Nutr. 2023 Apr 14;129(7):1136-1141. doi: 10.1017/S0007114522002252. Epub 2022 Aug 1.
Compared with an omnivorous Western diet, plant-based diets containing mostly fruits, vegetables, grains, legumes, nuts and seeds, with restricted amounts of foods of animal origin, are associated with reduced risk and severity of COVID-19. Additionally, inflammatory immune responses and severe acute respiratory symptoms of COVID-19, including pulmonary oedema, shortness of breath, fever and nasopharyngeal infections, are associated with Na toxicity from excessive dietary Na. High dietary Na is also associated with increased risks of diseases and conditions that are co-morbid with COVID-19, including chronic kidney disease, hypertension, stroke, diabetes and obesity. This article presents evidence that low dietary Na potentially mediates the association of plant-based diets with COVID-19 prevention. Processed meats and poultry injected with sodium chloride contribute considerable amounts of dietary Na in the Western diet, and the avoidance or reduction of these and other processed foods in whole-food plant-based (WFPB) diets could help lower overall dietary Na intake. Moreover, high amounts of K in plant-based diets increase urinary Na excretion, and preagricultural diets high in plant-based foods were estimated to contain much lower ratios of dietary Na to K compared with modern diets. Further research should investigate low Na in WFPB diets for protection against COVID-19 and co-morbid conditions.
46The Role of Dietary Potassium in the Cardiovascular Protective Effects of Plant-Based Diets.PubMed
Olgert Bardhi, Deborah J Clegg, Biff F Palmer
Semin Nephrol. 2023 Mar;43(2):151406. doi: 10.1016/j.semnephrol.2023.151406. Epub 2023 Aug 4.
Dietary intervention is an essential factor in managing a multitude of chronic health conditions such as cardiovascular and chronic kidney disease. In recent decades, there has been a host of research suggesting the potential benefit of plant-based diets in mitigating the health outcomes of these conditions. Plant-based diets are rich in vegetables and fruits, while limiting processed food and animal protein sources. The underlying physiological mechanism involves the interaction of several macronutrients and micronutrients such as plant protein, carbohydrates, and dietary potassium. Specifically, plant-based foods rich in potassium provide cardiorenal protective effects to include urinary alkalization and increased sodium excretion. These diets induce adaptive physiologic responses that improve kidney and cardiovascular hemodynamics and improve overall metabolic health. A shift toward consuming plant-based diets even in subjects with cardiorenal decrements may reduce their morbidity and mortality. Nonetheless, randomized controlled trials are needed to confirm the clinical benefits of plant-based diets.
47Origins and evolution of the Western diet: health implications for the 21st century.PubMed
Loren Cordain, S Boyd Eaton, Anthony Sebastian, et al.
Am J Clin Nutr. 2005 Feb;81(2):341-54. doi: 10.1093/ajcn.81.2.341.
There is growing awareness that the profound changes in the environment (eg, in diet and other lifestyle conditions) that began with the introduction of agriculture and animal husbandry approximately 10000 y ago occurred too recently on an evolutionary time scale for the human genome to adjust. In conjunction with this discordance between our ancient, genetically determined biology and the nutritional, cultural, and activity patterns of contemporary Western populations, many of the so-called diseases of civilization have emerged. In particular, food staples and food-processing procedures introduced during the Neolithic and Industrial Periods have fundamentally altered 7 crucial nutritional characteristics of ancestral hominin diets: 1) glycemic load, 2) fatty acid composition, 3) macronutrient composition, 4) micronutrient density, 5) acid-base balance, 6) sodium-potassium ratio, and 7) fiber content. The evolutionary collision of our ancient genome with the nutritional qualities of recently introduced foods may underlie many of the chronic diseases of Western civilization.
48Sodium monitoring in commercially processed and restaurant foods.PubMed
Jaspreet K C Ahuja, Pamela R Pehrsson, David B Haytowitz, et al.
Am J Clin Nutr. 2015 Mar;101(3):622-31. doi: 10.3945/ajcn.114.084954. Epub 2015 Jan 28.
BACKGROUND: Most sodium in the US diet comes from commercially processed and restaurant foods. Sodium reduction in these foods is key to several recent public health efforts. OBJECTIVE: The objective was to provide an overview of a program led by the USDA, in partnership with other government agencies, to monitor sodium contents in commercially processed and restaurant foods in the United States. We also present comparisons of nutrients generated under the program to older data. DESIGN: We track ∼125 commercially processed and restaurant food items ("sentinel foods") annually using information from food manufacturers and periodically by nationwide sampling and laboratory analyses. In addition, we monitor >1100 other commercially processed and restaurant food items, termed "priority-2 foods" (P2Fs) biennially by using information from food manufacturers. These foods serve as indicators for assessing changes in the sodium content of commercially processed and restaurant foods in the United States. We sampled all sentinel foods nationwide and reviewed all P2Fs in 2010-2013 to determine baseline sodium concentrations. RESULTS: We updated sodium values for 73 sentinel foods and 551 P2Fs in the USDA's National Nutrient Database for Standard Reference (releases 23-26). Sodium values changed by at least 10% for 43 of the sentinel foods, which, for 31 foods, including commonly consumed foods such as bread, tomato catsup, and potato chips, the newer sodium values were lower. Changes in the concentrations of related nutrients (total and saturated fat, total sugar, potassium, or dietary fiber) that were recommended by the 2010 Dietary Guidelines for Americans for reduced or increased consumption accompanied sodium reduction. The results of sodium reduction efforts, based on resampling of the sentinel foods or re-review of P2Fs, will become available beginning in 2015. CONCLUSION: This monitoring program tracks sodium reduction efforts, improves food composition databases, and strengthens national nutrition monitoring.
49Nutritional and health benefits and risks of plant-based substitute foods.PubMed
François Mariotti
Proc Nutr Soc. 2025 Feb;84(1):110-123. doi: 10.1017/S0029665123004767. Epub 2023 Oct 26.
Plant-based substitutes (PBS) are seen as a convenient way to transition to a more plant-based diet, but their potential health benefits and nutritional concerns remain debated. Based on a review of the literature, it is concluded here that the primary risk of insufficient nutrient intake with PBS concerns iron and calcium, which are critical to the nutritional value of PBS. Other risks were identified but these would depend on the characteristics of the overall diet, as is the case for iodine in a diet containing no seafood or dairy, and vitamin B12 in a vegetarian/vegan diet. Conversely, the use of PBS is also expected to confer some benefits for long-term health because it would result in higher fibre intakes (in the case of meat PBS) and lower SFA intakes (but higher PUFA/MUFA intakes), but attention should be paid to a potential increase in sodium intake with PBS of meat products. In fact, a recurring finding in this review was that PBS is a very heterogeneous food category involving considerable variations in ingredient and nutrient composition, and whose design could be improved in order to foster nutritional and health benefits. The latter also depend on the animal food that is being replaced and are only deemed likely when PBS replace red meat. The fortification of PBS with key nutrients such as iron and calcium may constitute an actionable public health solution to further shift the balance in favour of PBS in the context of the current dietary transition in western countries.
50Ultra-Processed Food Consumption and Relation with Diet Quality and Mediterranean Diet in Southern Italy.PubMed
Justyna Godos, Francesca Giampieri, Wahidah H Al-Qahtani, et al.
Int J Environ Res Public Health. 2022 Sep 9;19(18):11360. doi: 10.3390/ijerph191811360.
Ultra-processed food (UPF) consumption has been the focus of major attention due to their potential effects on human health. The aim of this study was to investigate the intake of UPFs in a sample of southern Italian individuals and assess its relationship with nutrient profile and dietary quality parameters. A cross-sectional study was conducted on 1936 individuals older than 18 years randomly selected from the general population. A total of 110 food times have been categorized based on the level of processing using the NOVA classification. The average daily energy intake of the sample was 2091.1 kcal, 38.7% of which were from the NOVA group of unprocessed/minimally processed foods, 5.7% from processed culinary ingredients, 38.3% from processed foods, and 17.9% from the UPFs group. UPFs were more consumed among young, unmarried individuals, with high cultural level, smokers, and often eating out of home. The mean energy share of UPFs varied from 6.3% of total daily energy intake for individuals in the lowest quintile of UPF consumption to 34.2% for those in the upper quintile. Within the UPF group, the highest energy contribution was provided by fast foods and sweets. Compared to the lowest quintile of UPF consumption, individuals in the highest quintile consumed, on average, additional 300 kcals per day and less fiber. Some plant-derived vitamins, such as vitamin A and vitamin C showed an inverse trend toward increasing shares of UPF consumption, while sodium intake increased. A significant higher intake of UPFs in individuals meeting the European and Italian dietary recommendations for carbohydrates, vitamin B12, vitamin D, and vitamin E was found, while UPFs were less consumed among those meeting the recommendations for total fats, fiber, sodium, potassium, and vitamin C. Finally, individuals displaying a "healthier" dietary profile, such as higher adherence to either the Mediterranean diet, the Dietary Approaches to Stop Hypertension, the Alternate Diet Quality Index, and the Diet Quality Index-International, consumed less UPFs and more unprocessed/minimally processed foods, with minor variation in the other NOVA food categories. In conclusion, consumption of UPF in southern Italy is in line with those reported in some other Mediterranean countries, although it negatively impacted the nutrient profile. It is important to monitor the consumption of UPFs before their availability and popularity put the grounds on younger generations' dietary habits.
51Impact of sodium intake on blood pressure, mortality and major cardiovascular events: an umbrella review of systematic reviews and meta-analyses.PubMed
Qiuyu Yang, Robin W M Vernooij, Hongfei Zhu, et al.
Crit Rev Food Sci Nutr. 2025;65(28):5903-5913. doi: 10.1080/10408398.2024.2434166. Epub 2024 Dec 3.
A plethora of systematic reviews with meta-analyses (SRMAs) evaluating sodium intake on cardiovascular health have been published. However, the quality of the SRMAs, that report absolute estimates of effect for major cardiovascular events and the corresponding certainty of the evidence has not been explicitly summarized. We conducted an umbrella review to assess the strength and validity of associations between lower sodium intake and cardiovascular outcomes. We used a modified, more stringent, version of the AMSTAR 2 instrument and the GRADE approach to assess SRMA methodological quality and evidence certainty, respectively. Across three cardiovascular risk strata, we computed the absolute risk reduction (ARR) for binary outcomes. We included 56 SRMAs. In various cardiovascular risk populations, moderate to high certainty evidence suggested that lower sodium intake reduced systolic blood pressure (BP) by -8.69 to -2.00 mmHg, and had concordant but smaller effects on diastolic BP. Salt substitutes conferred a small but important reduction in all-cause and cardiovascular mortality [ARR 12 fewer per 1000; 9 fewer per 1000; respectively], and had little to no effect on the risk of stroke [ARR 1 fewer per 1000]. Moderate to high certainty evidence suggested that lower sodium intake is probably beneficial for the prevention of major cardiovascular events, especially in low cardiovascular risk populations.
52Cannibal crickets on a forced march for protein and salt.PubMed
Stephen J Simpson, Gregory A Sword, Patrick D Lorch, et al.
Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4152-6. doi: 10.1073/pnas.0508915103. Epub 2006 Mar 3.
Swarming and mass migration are spectacular and sometimes devastating features of the biology of various animal species. These phenomena are typically associated with actual or anticipated depletion of food resources after an increase in population density, but the mechanisms driving such collective movements are poorly understood. Here we reveal that insects in large, coordinated migratory bands consisting of millions of Mormon crickets in western North America were deprived of two essential nutritional resources: protein and salt. The insects themselves provided a major source of these nutrients, and cannibalism was rife. We show that protein and salt satiation reduced cannibalism and that protein satiation inhibited walking. Additionally, experimentally reducing the motility or mobility of crickets substantially increased their risk of being cannibalized by other band members. As a result, the availability of protein and salt in the habitat will influence the extent to which bands march, both through the direct effect of nutrient state on locomotion and indirectly through the threat of cannibalism by resource-deprived crickets approaching from the rear. The crickets are, in effect, on a forced march. Migratory band formation and subsequent mass movement, therefore, are manifestations of specific tradeoffs between the costs and benefits of group living. Bands afford antipredator benefits to individual group members. Group movement then mitigates the resulting costs of intraspecific competition, namely local depletion of nutritional resources and the associated increased risk of cannibalism.
53Lactation: some cardiovascular and metabolic consequences, and the mechanisms of lactose and ion secretion into milk.PubMed
M Peaker
Ciba Found Symp. 1976(45):87-101. doi: 10.1002/9780470720271.ch6.
Lactation causes increases in mammary blood flow, gastrointestinal blood flow and cardiac output in the rat, and the suckling-induced release of lactogenic anterior pituitary hormones probably causes these changes, directly or indirectly. Metabolic requirements of lactation in women are similar to those in other animals not artificially selected for a high milk yield but the physiological control of the relationship between milk secretion and nutrient availability is not well understood. The unusual composition of the aqueous phase of human milk (rich in lactose but poor in sodium and potassium ions) can be explained by the same basic mechanisms for secretion of lactose and ions as operate in other animals but with quantitative differences.
54Intake and hedonics of calcium and sodium during pregnancy and lactation in the rat.PubMed
M Leshem, T Levin, J Schulkin
Physiol Behav. 2002 Mar;75(3):313-22. doi: 10.1016/s0031-9384(01)00668-0.
These experiments sought to distinguish whether increased calcium intake during pregnancy and lactation in the rat is due to arousal of a specific calcium appetite, with altered taste hedonics, as occurs with sodium depletion, to reduced taste sensitivity, or to the hyperdipsia of reproduction. We find that, during pregnancy and lactation, CaCl(2) intake is not increased more (in fact less) than intakes of control tastants, MgCl(2) and quinine HCl, and multiparous dams do not have a greater calcium intake than primaparous dams. Changes in taste reactivity to CaCl(2) and to NaCl do not correlate with changes in intake of these minerals during pregnancy or lactation, suggesting that alterations in hedonics or sensitivity do not explain the increased intake of these minerals. Taken together with the increased intake of all the tastants, it may be that the increased intakes of calcium and sodium during reproduction are not due to respective specific appetites or to a general mineral appetite but rather to the reproduction-increased ingestion that may meet all the dam's increased mineral and nutrient requirements. Differences in the degree of increased intakes of tastes may be due to specific alterations in their transduction during reproduction.
55Nutrition or detoxification: why bats visit mineral licks of the Amazonian rainforest.PubMed
Christian C Voigt, Krista A Capps, Dina K N Dechmann, et al.
PLoS One. 2008 Apr 23;3(4):e2011. doi: 10.1371/journal.pone.0002011.
Many animals in the tropics of Africa, Asia and South America regularly visit so-called salt or mineral licks to consume clay or drink clay-saturated water. Whether this behavior is used to supplement diets with locally limited nutrients or to buffer the effects of toxic secondary plant compounds remains unclear. In the Amazonian rainforest, pregnant and lactating bats are frequently observed and captured at mineral licks. We measured the nitrogen isotope ratio in wing tissue of omnivorous short-tailed fruit bats, Carollia perspicillata, and in an obligate fruit-eating bat, Artibeus obscurus, captured at mineral licks and at control sites in the rainforest. Carollia perspicillata with a plant-dominated diet were more often captured at mineral licks than individuals with an insect-dominated diet, although insects were more mineral depleted than fruits. In contrast, nitrogen isotope ratios of A. obscurus did not differ between individuals captured at mineral lick versus control sites. We conclude that pregnant and lactating fruit-eating bats do not visit mineral licks principally for minerals, but instead to buffer the effects of secondary plant compounds that they ingest in large quantities during periods of high energy demand. These findings have potential implications for the role of mineral licks for mammals in general, including humans.
56The role of large mammalian herbivores in shaping and maintaining soil microbial communities of natural mineral licks: A case study on sika deer at the firebreak adjacent to the Sino-Russian border.PubMed
Peiying Wen, Feng Wu, Lei Bao, et al.
Ecol Evol. 2024 Feb 1;14(2):e10878. doi: 10.1002/ece3.10878. eCollection 2024 Feb.
Mineral licks are indispensable habitats to the life history of large mammal herbivores (LMH). Geophagy at licks may provide the necessary minerals for LMH, while LMH may be ecosystem engineers of licks by altering vegetation cover and soil physicochemical properties (SPCP). However, the precise relationship between the LMH and licks remains unclear. To clarify the geophagy function of licks for LMH and their influence on soil at licks, we recorded visitation patterns of sika deer around licks and compared SPCP and microbial communities with the surrounding matrix in a firebreak adjacent to the Sino-Russian border. Our study indirectly supports the "sodium supplementation" hypothesis. Proofs included (1) a significantly higher sodium, iron, and aluminum contents than the matrix, while lower carbon, nitrogen, and moisture contents; (2) significantly higher deer visitation during sodium-demand season (growing season), along with an avoidance of licks with high iron contents, which is toxic when overdose. The microbes at the licks differed from those at the matrix, mainly driven by low soil carbon and nitrogen and altered biogeochemical cycles. The microbial communities of licks are vulnerable because of their unstable state and susceptibility to SPCP changes. Structural equation modeling (SEM) clearly showed a much stronger indirect effect of deer on microbes at licks than at the matrix, especially for bacteria. Multiple deer behaviors at licks, such as grazing, trampling, and excretion, can indirectly shape and stabilize microbes by altering carbon and nitrogen input. Our study is the first to characterize soil microbial communities at mineral licks and demonstrate the processes by which LMH shapes those communities. More studies are required to establish a general relationship between the LMH and licks to promote the conservation of natural licks for wildlife.
57Mineral licks: motivational factors for visitation and accompanying disease risk at communal use sites of elk and deer.PubMed
Michael J Lavelle, Gregory E Phillips, Justin W Fischer, et al.
Environ Geochem Health. 2014 Dec;36(6):1049-61. doi: 10.1007/s10653-014-9600-0. Epub 2014 Apr 8.
Free-ranging cervids acquire most of their essential minerals through forage consumption, though occasionally seek other sources to account for seasonal mineral deficiencies. Mineral sources occur as natural geological deposits (i.e., licks) or as anthropogenic mineral supplements. In both scenarios, these sources commonly serve as focal sites for visitation. We monitored 11 licks in Rocky Mountain National Park, north-central Colorado, using trail cameras to quantify daily visitation indices (DVI) and soil consumption indices (SCI) for Rocky Mountain elk (Cervus elaphus) and mule deer (Odocoileus hemionus) during summer 2006 and documented elk, mule deer, and moose (Alces alces) visiting licks. Additionally, soil samples were collected, and mineral concentrations were compared to discern levels that explain rates of visitation. Relationships between response variables; DVI and SCI, and explanatory variables; elevation class, moisture class, period of study, and concentrations of minerals were examined. We found that DVI and SCI were greatest at two wet, low-elevation licks exhibiting relatively high concentrations of manganese and sodium. Because cervids are known to seek Na from soils, we suggest our observed association of Mn with DVI and SCI was a likely consequence of deer and elk seeking supplemental dietary Na. Additionally, highly utilized licks such as these provide an area of concentrated cervid occupation and interaction, thus increasing risk for environmental transmission of infectious pathogens such as chronic wasting disease, which has been shown to be shed in the saliva, urine, and feces of infected cervids.
58Phosphorus and sodium contents in commercial wet foods for dogs and cats.PubMed
Marcio A Brunetto, Rafael V A Zafalon, Fabio A Teixeira, et al.
Vet Med Sci. 2019 Nov;5(4):494-499. doi: 10.1002/vms3.183. Epub 2019 Jul 5.
It has been reported that wet foods for dogs and cats have high levels of sodium and phosphorus due to their composition. Therefore, this study aimed to evaluate the sodium and phosphorus contents in wet pet foods, and compare it to daily requirements for both species. Twenty-five commercial wet foods for adult animals were evaluated, 13 for dogs and 12 for cats. The analyses' results were compared to the European Pet Food Industry Federation (FEDIAF 2018) recommendations. All foods contained phosphorus and sodium amounts above minimum requirements. Three wet foods for dogs exceeded the safe upper limit for phosphorus, and four wet foods for dogs and three for cats exceeded 3.75 g of sodium/1,000 kcal metabolizable energy (ME), considered safe by FEDIAF. No studies were found at the present time evaluating whether higher sodium levels are safe for dogs and cats; however, consumption of high phosphorus diets has been associated with adverse effects on renal function parameters. Therefore, more studies are necessary to investigate the health implications of phosphorus and sodium concentrations observed in some foods evaluated in this research.
59Effects of crude protein and sodium intake on water turnover in cats fed extruded diets.PubMed
Caroline A Garcia, Bruna A Loureiro, Francine M Peres, et al.
J Anim Physiol Anim Nutr (Berl). 2021 Nov;105 Suppl 2:95-105. doi: 10.1111/jpn.13374. Epub 2020 Jun 17.
The comprehension of strategies to increase urine production may be important, especially in kibble diets to prevent urolithiasis in cats. The effects of increasing amounts of crude protein (CP) and sodium on the water turnover of cats were evaluated using the water balance (WB) method and the deuterium dilution technique. The study followed a randomized block design, with three blocks of eight cats, two cats per food type in each block, and six cats per food. Four extruded diets with different amounts of CP and sodium were evaluated (on DM basis): 28% CP and 0.58% sodium; 39% CP and 0.64% sodium; 52% CP and 0.76% sodium; and 64% CP and 0.87% sodium. Cats were individually housed in cages for 8 days to measure WB, urea excretion, and faecal and urine characteristics. Deuterium oxide was used to evaluate water turnover, and during the period cats were housed in a collective cattery. The data were analysed by an F test, and the means were compared by polynomial contrasts. The ɑ level of significance was set at 0.05. The methods were compared by Pearson correlation, and Bland and Altman analysis. The increase in the CP content elevated linearly the renal excretion of urea (p < .001), and, together with the higher sodium intake, elevated the renal solute load, which resulted in a linear increase in urine production and water intake (p < .01). The urine density, metabolic water, and faecal and insensible water losses did not differ (p > .05). The water flux increased linearly when using the deuterium method (p < .001), but the obtained values were 20.85 ± 11.11 ml/cat/day higher than those verified using the WB method (p = .001). Higher CP and sodium amounts in dry diets increased the urine production and water consumption of cats, and this can be explored as a possible option to increase urination.
60Renal structural flexibility in response to environmental water stress in feral hogs.PubMed
S M Zervanos, S Naveh
J Exp Zool. 1988 Sep;247(3):285-8. doi: 10.1002/jez.1402470313.
Several morphological characteristics of the kidney were studied to determine the degree of acclimatization that may occur in three groups of feral hogs raised under different environmental conditions. Two groups of hogs were living in the wild, while another was raised in captivity for three generations and was directly descended from one of the wild-living groups. The two groups of wild hogs were living under two different types of water stress conditions. One group experienced periodic drought, and the other ate a high salt diet. The captive hogs were given food and water ad libitum. The captive-raised hogs had significantly lower relative medullary thickness (RMT) and relative medullary area (RMA) values (RMT of 2.35; RMA of 0.35) than either group of hogs living in the wild (RMT of 2.70 and 2.69; RMA of 0.41 and 0.44). Since the feral hogs living in the wild were exposed to a higher degree of water stress than the captive-raised hogs, it was concluded that the differences in observed kidney structure were due to acclimatization.
61Sodium Intake and Heart Failure.PubMed
Yash Patel, Jacob Joseph
Int J Mol Sci. 2020 Dec 13;21(24):9474. doi: 10.3390/ijms21249474.
Sodium is an essential mineral and nutrient used in dietary practices across the world and is important to maintain proper blood volume and blood pressure. A high sodium diet is associated with increased expression of β-myosin heavy chain, decreased expression of α/β-myosin heavy chain, increased myocyte enhancer factor 2/nuclear factor of activated T cell transcriptional activity, and increased salt-inducible kinase 1 expression, which leads to alteration in myocardial mechanical performance. A high sodium diet is also associated with alterations in various proteins responsible for calcium homeostasis and myocardial contractility. Excessive sodium intake is associated with the development of a variety of comorbidities including hypertension, chronic kidney disease, stroke, and cardiovascular diseases. While the American College of Cardiology/American Heart Association/Heart Failure Society of America guidelines recommend limiting sodium intake to both prevent and manage heart failure, the evidence behind such recommendations is unclear. Our review article highlights evidence and underlying mechanisms favoring and contradicting limiting sodium intake in heart failure.
62The impact of excessive salt intake on human health.PubMed
Robert W Hunter, Neeraj Dhaun, Matthew A Bailey
Nat Rev Nephrol. 2022 May;18(5):321-335. doi: 10.1038/s41581-021-00533-0. Epub 2022 Jan 20.
Intake of salt is a biological imperative, inextricably woven into physiological systems, human societies and global culture. However, excessive salt intake is associated with high blood pressure. As this effect likely drives cardiovascular morbidity and mortality, excessive salt intake is estimated to cause ~5 million deaths per annum worldwide. Animal research has identified various mechanisms by which high salt intake drives disease in the kidney, brain, vasculature and immune system. The potential for therapeutic interventions in many of these pathways has yet to be tested. Salt-reduction interventions lower blood pressure, but for most individuals, 'hidden' salt in processed foods disconnects salt intake from discretionary control. This problem is compounded by growing inequalities in food systems, which form another hurdle to sustaining individual dietary control of salt intake. The most effective salt-reduction interventions have been implemented at the population level and comprise multi-component approaches, involving government, education and the food industry.
63Salt-Sensitive Hypertension and the Kidney.PubMed
Mitsuhiro Nishimoto, Karen A Griffin, Brandi M Wynne, et al.
Hypertension. 2024 Jun;81(6):1206-1217. doi: 10.1161/HYPERTENSIONAHA.123.21369. Epub 2024 Mar 28.
Salt-sensitive hypertension (SS-HT) is characterized by blood pressure elevation in response to high dietary salt intake and is considered to increase the risk of cardiovascular and renal morbidity. Although the mechanisms responsible for SS-HT are complex, the kidneys are known to play a central role in the development of SS-HT and the salt sensitivity of blood pressure (SSBP). Moreover, several factors influence renal function and SSBP, including the renin-angiotensin-aldosterone system, sympathetic nervous system, obesity, and aging. A phenotypic characteristic of SSBP is aberrant activation of the renin-angiotensin system and sympathetic nervous system in response to excessive salt intake. SSBP is also accompanied by a blunted increase in renal blood flow after salt loading, resulting in sodium retention and SS-HT. Obesity is associated with inappropriate activation of the aldosterone mineralocorticoid receptor pathway and renal sympathetic nervous system in response to excessive salt, and mineralocorticoid receptor antagonists and renal denervation attenuate sodium retention and inhibit salt-induced blood pressure elevation in obese dogs and humans. SSBP increases with age, which has been attributed to impaired renal sodium handling and a decline in renal function, even in the absence of kidney disease. Aging-associated changes in renal hemodynamics are accompanied by significant alterations in renal hormone levels and renal sodium handling, resulting in SS-HT. In this review, we focus mainly on the contribution of renal function to the development of SS-HT.
64Dietary Protein, Chronic Salt-Sensitive Hypertension, and Kidney Damage.PubMed
David L Mattson, John Henry Dasinger, Justine M Abais-Battad
Kidney360. 2023 Aug 1;4(8):1181-1187. doi: 10.34067/KID.0000000000000210. Epub 2023 Jul 10.
It has been estimated that over a fifth of deaths worldwide can be attributed to dietary risk factors. A particularly serious condition is salt-sensitive (SS) hypertension and renal damage, participants of which demonstrate increased morbidity and mortality. Notably, a large amount of evidence from humans and animals has demonstrated that other components of the diet can also modulate hypertension and associated end-organ damage. Evidence presented in this review provides support for the view that immunity and inflammation serve to amplify the development of SS hypertension and leads to malignant disease accompanied by tissue damage. Interestingly, SS hypertension is modulated by changes in dietary protein intake, which also influences immune mechanisms. Together, the evidence presented in this review from animal and human studies indicates that changes in dietary protein source have profound effects on the gut microbiota, microbiota-derived metabolites, gene expression, immune cell activation, the production of cytokines and other factors, and the development of SS hypertension and kidney damage.
65Cardioprotection and lifespan extension by the natural polyamine spermidine.PubMed
Tobias Eisenberg, Mahmoud Abdellatif, Sabrina Schroeder, et al.
Nat Med. 2016 Dec;22(12):1428-1438. doi: 10.1038/nm.4222. Epub 2016 Nov 14.
Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.
66Sodium intake, RAAS-blockade and progressive renal disease.PubMed
Martin H de Borst, Gerjan Navis
Pharmacol Res. 2016 May;107:344-351. doi: 10.1016/j.phrs.2016.03.037. Epub 2016 Mar 31.
Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the renal protective effect of RAAS-blockade is incomplete. Short-term clinical studies have demonstrated that dietary sodium restriction potentiates the antiproteinuric effect of RAAS-blockade. More recently, it was shown that this effect is accompanied by a lower risk of end-stage renal disease and adverse cardiovascular outcomes. The modulation of RAAS-blockade efficacy by sodium intake is likely multifactorial, and is mediated by effects of sodium on local tissue RAAS in kidney, vasculature and brain, and by effects on the immune system. Despite the evidence showing the beneficial effects of even a moderate sodium restriction (∼2.5g/d), it remains difficult to realize in clinical practice. In an analysis based on 24-h urinary sodium excretion data from more than 10,000 CKD patients and renal transplant recipients, we found that sodium intake in these patients is on average 3.8g/d, closely resembling the global general population (3.95g/d). Behavioral approaches including the use of online dietary coaching (ehealth) and feedback using data from 24-h urine collections may be useful to successfully lower dietary sodium intake, aiming to improve cardio-renal outcomes in patients with CKD.
67A novel model of cardiovascular-kidney-metabolic syndrome combining unilateral nephrectomy and high-salt-sugar-fat diet in mice.PubMed
Lucas Rannier R A Carvalho, Miho Shimari, Ariela Maína Boeder, et al.
Lab Anim (NY). 2024 Nov;53(11):336-346. doi: 10.1038/s41684-024-01457-5. Epub 2024 Oct 22.
The aim of this study was to explore biological interaction and pathophysiology mechanisms in a new mouse model of cardiovascular-kidney-metabolic (CKM) syndrome, induced by chronic moderate renal failure in combination with consumption of a customized Western diet rich in carbohydrates, fat and salt. Male C57BL/6J mice were subjected to unilateral nephrectomy, fed a customized Western diet rich not only in sugar and fat but also in salt, and followed for 12 weeks or 20 weeks. Sham-operated mice on a standard chow served as healthy controls. Body composition, weight gain, glucose metabolism, fat distribution, blood pressure, cardiac function, vascular reactivity, renal function, inflammation and mitochondrial function were measured and combined with biochemical and histopathological analyses. The novel triple-hit model of CKM syndrome showed signs and symptoms of metabolic syndrome, disturbed glucose metabolism, impaired adipocyte physiology and fat redistribution, cardiovascular dysfunction, renal damage and dysfunction, systemic inflammation, elevated blood pressure and cardiac remodeling. The pathological changes were more pronounced in mice after prolonged exposure for 20 weeks, but no deaths occurred. In the present mouse model of CKM syndrome, profound and significant metabolic, cardiac, vascular and renal dysfunctions and injuries emerged by using a Western diet rich not only in fat and carbohydrates but also in salt. This multisystem disease model could be used for mechanistic studies and the evaluation of new therapeutic strategies.
68Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells.PubMed
Markus Kleinewietfeld, Arndt Manzel, Jens Titze, et al.
Nature. 2013 Apr 25;496(7446):518-22. doi: 10.1038/nature11868. Epub 2013 Mar 6.
There has been a marked increase in the incidence of autoimmune diseases in the past half-century. Although the underlying genetic basis of this class of diseases has recently been elucidated, implicating predominantly immune-response genes, changes in environmental factors must ultimately be driving this increase. The newly identified population of interleukin (IL)-17-producing CD4(+) helper T cells (TH17 cells) has a pivotal role in autoimmune diseases. Pathogenic IL-23-dependent TH17 cells have been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, and genetic risk factors associated with multiple sclerosis are related to the IL-23-TH17 pathway. However, little is known about the environmental factors that directly influence TH17 cells. Here we show that increased salt (sodium chloride, NaCl) concentrations found locally under physiological conditions in vivo markedly boost the induction of murine and human TH17 cells. High-salt conditions activate the p38/MAPK pathway involving nuclear factor of activated T cells 5 (NFAT5; also called TONEBP) and serum/glucocorticoid-regulated kinase 1 (SGK1) during cytokine-induced TH17 polarization. Gene silencing or chemical inhibition of p38/MAPK, NFAT5 or SGK1 abrogates the high-salt-induced TH17 cell development. The TH17 cells generated under high-salt conditions display a highly pathogenic and stable phenotype characterized by the upregulation of the pro-inflammatory cytokines GM-CSF, TNF-α and IL-2. Moreover, mice fed with a high-salt diet develop a more severe form of EAE, in line with augmented central nervous system infiltrating and peripherally induced antigen-specific TH17 cells. Thus, increased dietary salt intake might represent an environmental risk factor for the development of autoimmune diseases through the induction of pathogenic TH17 cells.
69Sodium chloride triggers Th17 mediated autoimmunity.PubMed
Stefanie Haase, Nicola Wilck, Markus Kleinewietfeld, et al.
J Neuroimmunol. 2019 Apr 15;329:9-13. doi: 10.1016/j.jneuroim.2018.06.016. Epub 2018 Jun 30.
The detrimental effects of a high-salt diet on human health have received much attention in the past few years. While it has been well established that high dietary salt intake is related to cardiovascular diseases, there is growing evidence that excess salt also affects the immune system and might be considered as a risk factor in autoimmune diseases such as multiple sclerosis (MS). Several studies have implicated T helper 17 cells (Th17) in the pathogenesis of MS. We and others recently demonstrated that excessive salt enhances the differentiation of Th17 cells, inducing a highly pathogenic phenotype that aggravates experimental neuroinflammation. Moreover, a diet rich in sodium affects intestinal microbiota alongside increased intestinal Th17 cells, thus linking the detrimental effects of high salt consumption to the gut-immune axis. First human studies revealed an association of increased MS disease activity with elevated sodium chloride consumption, while more recent epidemiology studies in larger cohorts suggest no correlation between salt intake and MS. However, it is known that ordinary urinary sodium analyses and nutritional questionnaires do not necessarily correspond to the actual sodium load and more sophisticated analyses are needed. Moreover, studies revealed that sodium can temporarily be stored in the body. This review summarizes recent findings on the impact of salt on the immune system and discusses potential challenges investigating dietary salt intake as a risk factor in MS.
70Sodium chloride, SGK1, and Th17 activation.PubMed
Katrina J Binger, Ralf A Linker, Dominik N Muller, et al.
Pflugers Arch. 2015 Mar;467(3):543-50. doi: 10.1007/s00424-014-1659-z. Epub 2014 Dec 4.
The incidence of autoimmune diseases in Western civilizations is increasing rapidly, suggesting an influence of environmental factors, such as diet. The pathogenesis of several of these autoimmune diseases is characterized by aberrant activation of T helper 17 (Th17) cells. Recent reports have shown that the differentiation of Th17 cells is sensitive to changes in local microenvironments, in particular salt (NaCl) concentrations, in a molecular mechanism centered around the serum- and glucocorticoid-inducible kinase 1 (SGK1). In this review, we summarize the recently disclosed mechanisms by which salt has been shown to affect SGK1 and, subsequently, Th17 activation.
71High-salt-driven gut microbiota dysfunction aggravates prostatitis by promoting AHR/SGK1/FOXO1 axis-mediated Th17 cell differentiation.PubMed
Jing Chen, Rui Feng, Bin-Bin Gong, et al.
Mil Med Res. 2025 May 19;12(1):21. doi: 10.1186/s40779-025-00607-1.
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain. Proinflammatory T helper 17 (Th17) cells are essential for triggering the development of CP/CPPS. High-salt diet (HSD) consumption has been found to cause an accumulation of sodium chloride in peripheral organs, inducing autoimmune responses via the Th17 cell axis. It is currently unknown whether HSD affects the etiology and course of CP/CPPS. METHODS: Patients diagnosed with CP/CPPS were evaluated with the National Institutes of Health Chronic Prostatitis Symptom Index scoring system, and the correlation between the symptoms of CP/CPPS with HSD was analyzed. The experimental autoimmune prostatitis (EAP) mouse was established and the mice were fed either a normal-salt diet (NSD) or HSD for 6 weeks to investigate the impact of HSD on CP/CPPS. Then, 16S ribosomal RNA sequencing and untargeted metabolomics were introduced to detect the differences in the gut microflora composition and metabolite profiles between NSD-fed and HSD-fed mice, followed by fecal microbiota transplantation, 5-hydroxyindole acetic acid (5-HIAA) supplementation, aryl hydrocarbon receptor (AHR) inhibition, and in vitro Th17 differentiation experiments, which were performed to explore the mechanisms underlying HSD-aggravated CP/CPPS. Finally, chromatin immunoprecipitation assay and quantitative polymerase chain reaction were conducted to validate whether AHR can serve as a transcription factor by interacting with the serum and glucocorticoid-regulated kinase 1 (Sgk1) promoter in CD4 T cells. RESULTS: Increased salt consumption had a positive correlation with symptom scores of CP/CPPS patients, which was validated by feeding EAP mice with HSD, and HSD worsened the prostate inflammation and tactile allodynia in EAP mice through promoting the differentiation of CD4 T cells to Th17 cells. HSD exacerbated EAP by significantly reducing the relative abundance of beneficial gut microflora, such as Lactobacillaceae, and gut microbiota metabolite 5-HIAA, which is related to tryptophan metabolism. The prostate inflammation, tactile allodynia, and proportion of Th17 cells in mice that received fecal suspensions from the EAP + HSD group were significantly more severe or higher than those in mice that received fecal suspensions from the EAP + NSD group. However, 5-HIAA supplementation ameliorated the symptoms of EAP caused by HSD through inhibiting the differentiation of CD4 T cells to Th17 cells, while AHR inhibition abrogated the protective effects of 5-HIAA supplementation on EAP mice fed a HSD through promoting the differentiation of CD4 T cells to Th17 cells. Mechanistically, it has been revealed that the SGK1/forkhead box protein O1 (FOXO1) pathway was significantly activated during cytokine-induced Th17 cell differentiation, and AHR has been shown to inhibit SGK1 transcription by interacting with the Sgk1 promoter in CD4 T cells to inhibit FOXO1 phosphorylation, consequently restoring the equilibrium of Th17 cell differentiation. CONCLUSION: Our findings indicated that high salt intake represented a risk factor for the development of CP/CPPS as it promoted the differentiation of CD4 T cells to Th17 cells through the 5-HIAA/AHR/SGK1/FOXO1 axis, which might be a potential therapeutic target for CP/CPPS.
72High-salt diet drives depression-like behavior in mice by inducing IL-17A production.PubMed
Di Lu, Wenjie Chen, Wenhui Sun, et al.
J Immunol. 2025 Apr 1;214(4):624-635. doi: 10.1093/jimmun/vkaf019.
Major depression disorder is a common illness that severely limits psychosocial functioning, affects outcomes of other diseases, and diminishes the quality of life. High-salt diet (HSD) has long been closely associated with the occurrence and development of depression, but whether or how HSD causes depression remains unclear. In this study, HSD induces depression-like behavior in mice accompanied by an increase in IL-17A production. RORγt deficiency abolishes HSD-induced depression-like behavior in mice. Furthermore, γδT17 cells are identified as an important cellular source of IL-17A in mice with HSD-induced depression. Depletion of γδT cells using anti-TCRγδ antibody markedly alleviates depression-like behavior in mice with HSD. Our findings demonstrate that increased dietary salt intake facilitates the development of depression at least partially through the induction of γδT17 cells.
73Moderator's view: Salt, cardiovascular risk, observational research and recommendations for clinical practice.PubMed
Carmine Zoccali, Francesca Mallamaci
Nephrol Dial Transplant. 2016 Sep;31(9):1405-8. doi: 10.1093/ndt/gfw277. Epub 2016 Aug 3.
In observational studies, blood pressure (BP), cholesterol and nutritional status biomarkers, including sodium intake, coherently show a J- or U-shaped relationship with health outcomes. Yet these data may reflect a stable sodium intake or a reduced intake due to comorbidities or intercurrent disease, or an intentional decrease in salt intake. Adjusting for comorbidities and risk factors may fail to eliminate confounding. For cholesterol and BP, we base our recommendations for prevention and treatment on interventional (experimental) studies. For sodium, we lack the perfect large-scale trial we would need, but substantial circumstantial information derived from interventional studies cannot be ignored. The objection that modelling the risk of salt excess for cardiovascular disease events based on the effect of salt intake on BP is unjustified fails to consider a recent meta-analysis showing that, independently of the intervention applied, intensive BP-lowering treatment (average BP 133/76 mmHg), compared with the less intensive treatment (140/81 mmHg), is associated with a 14% risk reduction for major cardiovascular events. In this knowledge context, inertia, i.e. awaiting the 'mother trial', is not justified. While recognizing that this trial may still be needed and that actual data, rather than modelled data, are the ideal solution, for now, the World Health Organization recommendation of reducing salt intake to <2 g/day of sodium (5 g/day of salt) in adults stands.
74PubMed
This guideline provides updated global, evidence-informed recommendations on the consumption of sodium to reduce NCDs in most adults and children. The recommendations in this guideline can be used by policy-makers, technical and programme planners in the government and various organizations involved in the design, implementation and scaling-up of nutrition actions for public health and prevention of NCDs, to assess current sodium intake levels relative to a benchmark and develop measures to decrease sodium intake, where necessary, through public health interventions including, reducing content in manufactured food, food and product labelling, consumer education, and the establishment of food-based dietary guidelines (FBDG). The guideline should be should be used in conjunction with potassium and other nutrient guidelines to develop and guide national policies and public health nutrition programmes. The reduction of sodium intake in the population is a cost-effective public health intervention for preventing NCDs and is one of the nine global targets selected by Member States for the prevention and control of NCDs.
75Global guidelines recommendations for dietary sodium and potassium intake.PubMed
Ebtehal Salman, Aya Kadota, Katsuyuki Miura
Hypertens Res. 2024 Jun;47(6):1620-1626. doi: 10.1038/s41440-024-01663-1. Epub 2024 Apr 8.
Non-communicable diseases (NCDs) cause a significant global health challenge, with unhealthy diets identified as a major risk factor. Sodium and potassium, which are essential minerals for human health, play important roles in various bodily functions, and an imbalance in their intake can have significant health implications, particularly concerning hypertension and cardiovascular diseases. This review compiles dietary sodium and potassium intake recommendations from prominent global health organizations and compares global guidelines to Japan's Dietary Reference Intake (DRI) guidelines. Sodium and potassium intake guidelines from organizations such as the World Health Organization (WHO), American College of Cardiology (ACC) and American Heart Association (AHA), Dietary Guidelines for Americans (DGA), European Food Safety Authority (EFSA), and DRI for Japanese exhibit variations. Compared to other Asian countries, Japan's historically higher sodium goal aligns with Southeast Asia where traditional preserved foods contribute to high sodium intake. Contrarily, Japan's lower potassium goal contrasts with other countries in Asia promoting a diet rich in fruits and vegetables. The ongoing effort by Japan to align with global recommendations reflects a gradation approach considering social habits. While harmonizing international efforts is essential, appreciating regional diversities is paramount through tailoring guidelines to cultural and dietary habit practices. Implementing context-specific guidelines informed by scientific research can contribute to global efforts in promoting healthy diets and reducing the burden of NCDs. Global guidelines that recommended the daily dietary intake goal for sodium and potassium exhibit variations. These disparities are influenced by diverse factors, including cultural dietary habits, socioeconomic status, health priorities, and available scientific research. Each population should follow the recommendations of their region.
76Global Drinking Water Standards Lack Clear Health-Based Limits for Sodium.PubMed
Juliette Crowther, Aliyah Palu, Alicia Dunning, et al.
Nutrients. 2025 Jun 30;17(13):2190. doi: 10.3390/nu17132190.
BACKGROUND/OBJECTIVES: High sodium consumption increases the risk of hypertension and cardiovascular disease. Although food remains the primary source of intake, elevated sodium levels in drinking water can further contribute to excessive intake, particularly in populations already exceeding recommendations. This review examines the extent to which national drinking water standards account for sodium-related health risks and aims to inform discussion on the need for enforceable, health-based sodium limits. METHODS: National standards for unbottled drinking water in 197 countries were searched for using the WHO 2021 review of drinking water guidelines, the FAOLEX database, and targeted internet and AI searches. For each country, data were extracted for the document name, year, regulatory body, regulation type, sodium limit (if stated), and rationale. Socio-geographic data were sourced from World Bank Open Data. A descriptive analysis was conducted using Microsoft Excel. RESULTS: Standards were identified for 164 countries. Of these, 20% ( = 32), representing 30% of the global population, had no sodium limit. Among the 132 countries with a sodium limit, 92% ( = 121) adopted the WHO's palatability-based guideline of 200 mg/L. Upper limits ranged from 50 to 400 mg/L. Only twelve countries (9%) cited health as a rationale. Three countries-Australia, Canada, and the United States-provided a separate recommendation for at-risk populations to consume water with sodium levels below 20 mg/L. CONCLUSIONS: Globally, drinking water standards give inadequate attention to sodium's health risks. Most either lack sodium limits or rely on palatability thresholds that are too high to protect health. Updating national and international standards to reflect current evidence is essential to support sodium reduction efforts. Health-based sodium limits would empower communities to better advocate for safe water. Amid rising water salinity, such reforms must be part of a broader global strategy to ensure universal and equitable access to safe, affordable drinking water as a basic human right.
77Obesity, Sodium Homeostasis, and Arterial Hypertension in Children and Adolescents.PubMed
Małgorzata Wójcik, Agnieszka Kozioł-Kozakowska
Nutrients. 2021 Nov 11;13(11):4032. doi: 10.3390/nu13114032.
BACKGROUND: The relationship between obesity, arterial hypertension, and excessive salt intake has been known for a long time; however, the mechanism of this relationship remains not clear. METHODS: The paper presents a current literature review on the relationship between salt consumption and the development of arterial hypertension in children and adolescents with obesity. RESULTS: In addition to the traditional theory of hypertension development due to the increase in intravascular volume and disturbances of sodium excretion, recent studies indicate the existence of a complex mechanism related to excessive, pathological secretory activity of adipocytes, insulin resistance, and impaired function of the renin-angiotensin-aldosterone axis. That makes obese children and adolescents particularly vulnerable to the development of salt-sensitive arterial hypertension. Studies performed in many countries have shown that children and adolescents consume more sodium than recommended. It is worth noting, however, that the basis for these recommendations was the extrapolation of data from studies conducted on adults. Moreover, more important than sodium intake is the Na/K ratio and water consumption. CONCLUSION: Regardless of the population-wide recommendations on reducing salt intake in children, specific recommendations for overweight and obese patients should be developed.
78Replacing salt with low-sodium salt substitutes (LSSS) for cardiovascular health in adults, children and pregnant women.PubMed
Amanda Brand, Marianne E Visser, Anel Schoonees, et al.
Cochrane Database Syst Rev. 2022 Aug 10;8(8):CD015207. doi: 10.1002/14651858.CD015207.
BACKGROUND: Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium contribute to elevated blood pressure. The WHO recommends decreasing mean population sodium intake through effective and safe strategies to reduce hypertension and its associated disease burden. Incorporating low-sodium salt substitutes (LSSS) into population strategies has increasingly been recognised as a possible sodium reduction strategy, particularly in populations where a substantial proportion of overall sodium intake comes from discretionary salt. The LSSS contain lower concentrations of sodium through its displacement with potassium predominantly, or other minerals. Potassium-containing LSSS can potentially simultaneously decrease sodium intake and increase potassium intake. Benefits of LSSS include their potential blood pressure-lowering effect and relatively low cost. However, there are concerns about potential adverse effects of LSSS, such as hyperkalaemia, particularly in people at risk, for example, those with chronic kidney disease (CKD) or taking medications that impair potassium excretion. OBJECTIVES: To assess the effects and safety of replacing salt with LSSS to reduce sodium intake on cardiovascular health in adults, pregnant women and children. SEARCH METHODS: We searched MEDLINE (PubMed), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 18 August 2021, and screened reference lists of included trials and relevant systematic reviews. No language or publication restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and prospective analytical cohort studies in participants of any age in the general population, from any setting in any country. This included participants with non-communicable diseases and those taking medications that impair potassium excretion. Studies had to compare any type and method of implementation of LSSS with the use of regular salt, or no active intervention, at an individual, household or community level, for any duration. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-text articles to determine eligibility; and extracted data, assessed risk of bias (RoB) using the Cochrane RoB tool, and assessed the certainty of the evidence using GRADE. We stratified analyses by adults, children (≤ 18 years) and pregnant women. Primary effectiveness outcomes were change in diastolic and systolic blood pressure (DBP and SBP), hypertension and blood pressure control; cardiovascular events and cardiovascular mortality were additionally assessed as primary effectiveness outcomes in adults. Primary safety outcomes were change in blood potassium, hyperkalaemia and hypokalaemia. MAIN RESULTS: We included 26 RCTs, 16 randomising individual participants and 10 randomising clusters (families, households or villages). A total of 34,961 adult participants and 92 children were randomised to either LSSS or regular salt, with the smallest trial including 10 and the largest including 20,995 participants. No studies in pregnant women were identified. Studies included only participants with hypertension (11/26), normal blood pressure (1/26), pre-hypertension (1/26), or participants with and without hypertension (11/26). This was unknown in the remaining studies. The largest study included only participants with an elevated risk of stroke at baseline. Seven studies included adult participants possibly at risk of hyperkalaemia. All 26 trials specifically excluded participants in whom an increased potassium intake is known to be potentially harmful. The majority of trials were conducted in rural or suburban settings, with more than half (14/26) conducted in low- and middle-income countries. The proportion of sodium chloride replacement in the LSSS interventions varied from approximately 3% to 77%. The majority of trials (23/26) investigated LSSS where potassium-containing salts were used to substitute sodium. In most trials, LSSS implementation was discretionary (22/26). Trial duration ranged from two months to nearly five years. We assessed the overall risk of bias as high in six trials and unclear in 12 trials. LSSS compared to regular salt in adults: LSSS compared to regular salt probably reduce DBP on average (mean difference (MD) -2.43 mmHg, 95% confidence interval (CI) -3.50 to -1.36; 20,830 participants, 19 RCTs, moderate-certainty evidence) and SBP (MD -4.76 mmHg, 95% CI -6.01 to -3.50; 21,414 participants, 20 RCTs, moderate-certainty evidence) slightly. On average, LSSS probably reduce non-fatal stroke (absolute effect (AE) 20 fewer/100,000 person-years, 95% CI -40 to 2; 21,250 participants, 3 RCTs, moderate-certainty evidence), non-fatal acute coronary syndrome (AE 150 fewer/100,000 person-years, 95% CI -250 to -30; 20,995 participants, 1 RCT, moderate-certainty evidence) and cardiovascular mortality (AE 180 fewer/100,000 person-years, 95% CI -310 to 0; 23,200 participants, 3 RCTs, moderate-certainty evidence) slightly, and probably increase blood potassium slightly (MD 0.12 mmol/L, 95% CI 0.07 to 0.18; 784 participants, 6 RCTs, moderate-certainty evidence), compared to regular salt. LSSS may result in little to no difference, on average, in hypertension (AE 17 fewer/1000, 95% CI -58 to 17; 2566 participants, 1 RCT, low-certainty evidence) and hyperkalaemia (AE 4 more/100,000, 95% CI -47 to 121; 22,849 participants, 5 RCTs, moderate-certainty evidence) compared to regular salt. The evidence is very uncertain about the effects of LSSS on blood pressure control, various cardiovascular events, stroke mortality, hypokalaemia, and other adverse events (very-low certainty evidence). LSSS compared to regular salt in children: The evidence is very uncertain about the effects of LSSS on DBP and SBP in children. We found no evidence about the effects of LSSS on hypertension, blood pressure control, blood potassium, hyperkalaemia and hypokalaemia in children. AUTHORS' CONCLUSIONS: When compared to regular salt, LSSS probably reduce blood pressure, non-fatal cardiovascular events and cardiovascular mortality slightly in adults. However, LSSS also probably increase blood potassium slightly in adults. These small effects may be important when LSSS interventions are implemented at the population level. Evidence is limited for adults without elevated blood pressure, and there is a lack of evidence in pregnant women and people in whom an increased potassium intake is known to be potentially harmful, limiting conclusions on the safety of LSSS in the general population. We also cannot draw firm conclusions about effects of non-discretionary LSSS implementations. The evidence is very uncertain about the effects of LSSS on blood pressure in children.
79Salt Substitution and Recurrent Stroke and Death: A Randomized Clinical Trial.PubMed
Xiong Ding, Xinyi Zhang, Liping Huang, et al.
JAMA Cardiol. 2025 Apr 1;10(4):343-350. doi: 10.1001/jamacardio.2024.5417.
IMPORTANCE: The direct effect of consumption of salt substitutes on recurrent stroke and mortality among patients with stroke remains unclear. OBJECTIVE: To evaluate the effects of salt substitutes vs regular salt on the incidence of recurrent stroke and mortality among patients with stroke. DESIGN, SETTING, AND PARTICIPANTS: The Salt Substitute and Stroke Study (SSaSS), an open-label, cluster randomized clinical trial, was conducted in 600 northern Chinese villages (clusters). Patients who self-reported a hospital diagnosis of stroke were included in this prespecified subgroup analysis. Data were analyzed from November 2023 to August 2024. INTERVENTIONS: Participants were assigned to use either a salt substitute, consisting of 75% sodium chloride and 25% potassium chloride by mass, or regular salt. MAIN OUTCOMES AND MEASURES: The primary outcome was recurrent stroke. RESULTS: After excluding 5746 persons without a baseline history of stroke, 15 249 patients with stroke (mean [SD] age, 64.1 [8.8] years; 6999 [45.9%] female; 8250 male [54.1%]) were included. Over a median (IQR) follow-up of 61.2 (60.9-61.6) months, the mean difference in systolic blood pressure was -2.05 mm Hg (95% CI, -3.03 to -1.08 mm Hg). A total of 2735 recurrent stroke events (691 fatal and 2044 nonfatal) and 3242 deaths were recorded. Recurrent stroke was significantly lower in the salt substitute vs regular salt group (rate ratio [RR], 0.86; 95% CI, 0.77-0.95; P = .005), with larger effects on hemorrhagic stroke (relative reduction, 30%; P = .002). Death rates were also significantly lower (RR, 0.88; 95% CI, 0.82-0.96; P = .003), with larger effects on stroke-related deaths (relative reduction 21%; P = .01). No significant difference was observed for hyperkalemia (RR, 1.01; 95% CI, 0.74-1.38; P = .96). CONCLUSIONS AND RELEVANCE: Results of this cluster trial demonstrate that salt substitution was safe, along with reduced risks of stroke recurrence and death, which underscores large health gains from scaling up this low-cost intervention among patients with stroke. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02092090.
80Salt substitution and salt-supply restriction for lowering blood pressure in elderly care facilities: a cluster-randomized trial.PubMed
Yifang Yuan, Aoming Jin, Bruce Neal, et al.
Nat Med. 2023 Apr;29(4):973-981. doi: 10.1038/s41591-023-02286-8. Epub 2023 Apr 13.
There is a paucity of high-quality evidence on the effectiveness and safety of salt reduction strategies, particularly for older people, who have the most to benefit but are at higher risk of adverse effects. Here, we conducted a clinical trial in which 48 residential elderly care facilities in China (1,612 participants including 1,230 men and 382 women, 55 years or older) were cluster-randomized using a 2 × 2 factorial design to provision of salt substitute (62.5% NaCl and 25% KCl) versus usual salt and to a progressively restricted versus usual supply of salt or salt substitute for 2 years. Salt substitute compared with usual salt lowered systolic blood pressure (-7.1 mmHg, 95% confidence interval (CI) -10.5 to -3.8), meeting the primary outcome of the trial, whereas restricted supply compared with usual supply of salt or salt substitute had no effect on systolic blood pressure. Salt substitute also lowered diastolic blood pressure (-1.9 mmHg, 95% CI -3.6 to -0.2) and resulted in fewer cardiovascular events (hazard ratio (HR) 0.60, 95% CI 0.38-0.96), but had no effect on total mortality (HR 0.84, 95% CI 0.63-1.13). From a safety standpoint, salt substitute increased mean serum potassium and led to more frequent biochemical hyperkalemia, but was not associated with adverse clinical outcomes. In contrast, salt restriction had no effect on any study outcome. The results of this trial indicate that use of salt substitute, but not efforts to restrict salt supply, may achieve blood pressure lowering and deliver health benefits to residents of elderly care facilities in China. Clinicaltrials.gov registration: NCT03290716.
81Effect of a Salt Substitute on Incidence of Hypertension and Hypotension Among Normotensive Adults.PubMed
Xianghui Zhang, Yifang Yuan, Chenglong Li, et al.
J Am Coll Cardiol. 2024 Feb 20;83(7):711-722. doi: 10.1016/j.jacc.2023.12.013.
BACKGROUND: Reports on the effects of salt substitution among individuals with normal blood pressure are scarce and controversial. OBJECTIVES: This study sought to assess the effects of a salt substitute (62.5% NaCl, 25% KCl, and 12.5% flavorings) on incidence of hypertension and hypotension among older adults with normal blood pressure. METHOD: A post hoc analysis was conducted among older adults with normal blood pressure participating in DECIDE-Salt, a large, multicenter, cluster-randomized trial in 48 elderly care facilities for 2 years. We used the frailty survival model to compare risk of incident hypertension and the generalized linear mixed model to compare risk of hypotension episodes. RESULTS: Compared with usual salt group (n = 298), the salt substitute group (n = 313) had a lower hypertension incidence (11.7 vs 24.3 per 100 person-years; adjusted HR: 0.60; 95% CI: 0.39 to 0.92; P = 0.02) but did not increase incidence of hypotension episodes (9.0 vs 9.7 per 100 person-years; P = 0.76). Mean systolic/diastolic blood pressure did not increase from the baseline to the end of intervention in the salt substitute group (mean changes: -0.3 ± 11.9/0.2 ± 7.1 mm Hg) but increased in the usual salt group (7.0 ± 14.3/2.1 ± 7.5 mm Hg), resulting in a net reduction of -8.0 mm Hg (95% CI: -12.4 to -3.7 mm Hg) in systolic and -2.0 mm Hg (95% CI: -4.1 to 0.1 mm Hg) in diastolic blood pressure between intervention groups. CONCLUSIONS: In Chinese older adults with normal blood pressure, replacing usual salt with a salt substitute may reduce the incidence of hypertension without increasing hypotension episodes. This suggests a desirable strategy for population-wide prevention and control of hypertension and cardiovascular disease, deserving further consideration in future studies. (Diet Exercise and Cardiovascular Health [DECIDE]-Salt Reduction Strategies for the Elderly in Nursing Homes in China [DECIDE-Salt]; NCT03290716).
82Sodium reduction in foods: Challenges and strategies for technical solutions.PubMed
Niklas Lorén, Jun Niimi, Evelina Höglund, et al.
J Food Sci. 2023 Mar;88(3):885-900. doi: 10.1111/1750-3841.16433. Epub 2023 Jan 19.
In many parts of the world, sodium consumption is higher than recommended levels, representing one of the most important food-related health challenges and leading to considerable economical costs for society. Therefore, there is a need to find technical solutions for sodium reduction that can be implemented by food producers and within food services. The aims of this review are to discuss the barriers related to sodium reduction and to highlight a variety of technical solutions. The barriers relate to consumer perception, microbiology, processing, and physicochemistry. Existing technical solutions include inhomogeneous salt distribution, coated salt particles, changing particle sizes and forms, surface coating, multisensory combinations, sodium replacements, double emulsions, adapted serum release by microstructure design, and adapted brittleness by microstructure design. These solutions, their implementation and the associated challenges, and applicable product categories are described. Some of these solutions are ready for use or are in their early development stages. Many solutions are promising, but in most cases, some form of adaptation or optimization is needed before application in specific products, and care must always be taken to ensure food safety. For instance, further research and innovation are required in the dynamic evolution of saltiness perception, consumer acceptance, the binding and migration of sodium, juiciness, microbiological safety, and the timing of salt addition during processing. Once implemented, these solutions will undoubtedly support food producers and food services in reducing sodium content and extend the application of the solutions to different foods.
83The food safety impact of salt and sodium reduction initiatives.PubMed
Deborah Christopher, Carol A Wallace
Perspect Public Health. 2014 Jul;134(4):216-24. doi: 10.1177/1757913914536701.
Excessive or high salt or sodium intake is known to cause hypertension and other diseases. Within the United Kingdom voluntary targets for salt reduction have been set and laid out in the Secretary of State responsibility deal. This review considers the options available to food manufacturers to enable them to reduce salt and the potential food safety risks associated with those options. Gaps in research and knowledge within the areas of information supplied to food manufacturers, alternative solutions for salt replacement and the food safety impact of salt reduction are discussed.
84Compendium of sodium reduction strategies in foods: A scoping review.PubMed
Aubrey N Dunteman, Elle N McKenzie, Ying Yang, et al.
Compr Rev Food Sci Food Saf. 2022 Mar;21(2):1300-1335. doi: 10.1111/1541-4337.12915. Epub 2022 Feb 24.
In response to health concerns generated by increased sodium intake, many new approaches have been studied to reduce the sodium content in processed food. It has been suggested that reducing sodium in the food supply may be the most appropriate solution. The aim of this scoping review was to establish what sodium reduction strategies are effective in maintaining acceptable sensory qualities for various food industry applications. Studies that evaluate and report on the effectiveness of a sodium reduction strategy relevant to food and included outcomes detailing how the strategies were received by human subjects using sensory data are included, as well as book chapters, literature reviews, and patents focusing on sodium reduction strategies. Only those published in English and since 1970 were included. Literature was obtained through Scopus, PubMed, EBSCOhost, and ScienceDirect databases, whereas patents were obtained through US Patent Trademark Office, Google Patents, and PATENTSCOPE databases. Two-hundred and seventy-seven primary studies, 27 literature reviews, 10 book chapters, and 143 patents were selected for inclusion. Data extracted included details such as analytical methods, broad and specific treatment categories, significant outcomes, and limitations among other material. Sodium reduction methods were categorized as either salt removal, salt replacement, flavor modification, functional modification, or physical modification. Although salt removal and salt replacement were the majority of included studies, future research would benefit from combining methods from other categories while investigating the impact on sensory characteristics, technological aspects, and consumer perception of the strategy.
85Influencers in Policy Fields on Social Media: Global Longitudinal Study of Dietary Sodium Reduction Posts, 2006-2022.PubMed
Alana Montoya, Lingchao Mao, Adam Drewnowski, et al.
J Med Internet Res. 2024 Dec 30;26:e54506. doi: 10.2196/54506.
BACKGROUND: Excessive sodium intake is a major concern for global public health. Despite multiple dietary guidelines, population sodium intakes are above recommended levels. Lack of health literacy could be one contributing issue and contemporary health literacy is largely shaped by social media. OBJECTIVE: This study aims to quantify the posting behaviors and influence patterns on dietary sodium-related content by influencers in the policy field on X (formerly Twitter) across time. METHODS: We first identified X users with a scope of work related to dietary sodium and retrieved their posts (formerly Tweets) from 2006 to 2022. Users were categorized into the policy groups of outer-setting organization, inner-setting organization, or individual, based on their role in the conceptual policy field. Network analysis was used to analyze interactions among users and identify the top influencers in each policy group. A 4D influence framework was applied to measure the overall influence, activity, priority, originality, and popularity scores. These measures were used to reveal the user-level, group-level, and temporal patterns of sodium-related influence. RESULTS: We identified 78 users with content related to dietary sodium, with 1,099,605 posts in total and 14,732 dietary sodium posts. There was an increasing volume of sodium posts from 2010 to 2015; however, the trend has been decreasing since 2016, especially among outer-setting organizations. The top influencers from the three policy groups were the World Health Organization (WHO), the American Heart Association, and Tom Frieden. Simon Capewell and the WHO ranked the highest in activity; the World Action on Salt, Sugar, and Health and Action on Salt had the highest priority for dietary sodium content; General Mills and Tom Frieden had the highest originality; and WHO, Harvard University School of Medicine, and Tom Frieden received the highest popularity. Outer-setting organizations tend to interact with more users in the network compared to inner-setting organizations and individuals, while inner-setting organizations tend to receive more engagements from other users in the network than the other two groups. Monthly patterns showed a significant peak in the number of sodium posts in March compared with other months. CONCLUSIONS: Despite the increased use of social media, recent trends of sodium intake education on social media are decreasing and the priority of sodium among other topics is low. To improve policy implementation effectiveness and meet recommended dietary targets, there is an increasing need for health leaders to consistently and collectively advocate for sodium intake reduction on social media.
86Sodium and Its Role in Cardiovascular Disease - The Debate Continues.PubMed
Yee Wen Kong, Sara Baqar, George Jerums, et al.
Front Endocrinol (Lausanne). 2016 Dec 23;7:164. doi: 10.3389/fendo.2016.00164. eCollection 2016.
Guidelines have recommended significant reductions in dietary sodium intake to improve cardiovascular health. However, these dietary sodium intake recommendations have been questioned as emerging evidence has shown that there is a higher risk of cardiovascular disease with a low sodium diet, including in individuals with type 2 diabetes. This may be related to the other pleotropic effects of dietary sodium intake. Therefore, despite recent review of dietary sodium intake guidelines by multiple organizations, including the dietary guidelines for Americans, American Diabetes Association, and American Heart Association, concerns about the impact of the degree of sodium restriction on cardiovascular health continue to be raised. This literature review examines the effects of dietary sodium intake on factors contributing to cardiovascular health, including left ventricular hypertrophy, heart rate, albuminuria, rennin-angiotensin-aldosterone system activation, serum lipids, insulin sensitivity, sympathetic nervous system activation, endothelial function, and immune function. In the last part of this review, the association between dietary sodium intake and cardiovascular outcomes, especially in individuals with diabetes, is explored. Given the increased risk of cardiovascular disease in individuals with diabetes and the increasing incidence of diabetes worldwide, this review is important in summarizing the recent evidence regarding the effects of dietary sodium intake on cardiovascular health, especially in this population.
87Relationship Between Salt Intake and Cardiovascular Disease.PubMed
Fuzhou Han, Wenqiang Li, Ning Duan, et al.
J Clin Hypertens (Greenwich). 2025 Jun;27(6):e70078. doi: 10.1111/jch.70078.
Cardiovascular disease (CVD) is a predominant global health issue, with dietary salt intake recognized as a crucial modifiable risk factor. This review elucidates the multifaceted relationship between salt consumption and CVD, exploring both its direct and indirect effects. While early research emphasized salt's influence on blood pressure, contemporary studies highlight the combined effects of dietary habits and genetic factors on CVD risk. The paper underscores the complex biological mechanisms linking high salt intake to CVD, including its impact on blood pressure, direct cardiovascular effects, immune responses, the role of prostanoids, epigenetic changes, and gut microbiome. Additionally, the review delves into the concept of salt sensitivity and its genetic underpinnings, emphasizing the heightened CVD risk in salt-sensitive individuals. The potential benefits and challenges of salt substitutes are also discussed. Drawing from various study designs, including epidemiological studies and randomized controlled trials, the review provides a comprehensive understanding of the detrimental effects of excessive salt intake on cardiovascular health, emphasizing the need for refined dietary guidelines and targeted interventions.