Zinc deficiency

Zinc deficiency is a nutritional disorder in which the amount of zinc available to the body is insufficient to meet physiological needs, and it affects the skin, gastrointestinal tract, immune system, skeleton, reproductive system and central nervous system.锌缺乏症是一种营养性疾病，指体内可利用的锌不足以满足生理需要，可累及皮肤、胃肠道、免疫系统、骨骼、生殖系统与中枢神经系统。

The condition arises when dietary intake falls short, when intestinal absorption is impaired, when losses increase or when demand rises, and reduced dietary intake is the most common cause worldwide.当膳食摄入不足、肠道吸收受损、丢失增加或需要量上升时可发生本病，其中膳食摄入不足是全球最常见的病因。

About 2.2 billion people are estimated to be affected, with preschool children and women of reproductive age in low- and middle-income countries carrying the largest burden.据估计全球约 22 亿人受累，低收入与中等收入国家的学龄前儿童及育龄女性负担最重。

Terminology and classification

• Zinc deficiency is the umbrella term for a negative zinc balance, whereas hypozincemia refers only to a serum zinc concentration below the reference range and can coexist with normal total-body zinc.锌缺乏症是锌负平衡的统称，而低锌血症仅指血清锌低于参考范围，可与体内总锌正常并存。
• ICD-10 codes the disorder as E60 within the chapter on endocrine, nutritional and metabolic diseases, and ICD-11 MMS assigns 5B5K.2 in the 2025-01 release.ICD-10 将其编码为 E60，归入内分泌、营养与代谢疾病章，ICD-11 MMS 2025-01 版将其编码为 5B5K.2。
• MeSH does not maintain a standalone descriptor for zinc deficiency and instead indexes the concept through the Zinc descriptor D015032 with the deficiency qualifier, a detail that matters when interoperability mappings are built.MeSH 没有为锌缺乏症单列主题词，而是通过锌主题词 D015032 加「缺乏」限定词进行标引，这一细节在构建互操作映射时很重要。
• UMLS assigns C0235950, the National Cancer Institute Thesaurus uses C97099 and Wikidata records the entity as Q8072298, which together support cross-database retrieval.UMLS 赋予 C0235950，美国国家癌症研究所词表使用 C97099，Wikidata 记录为 Q8072298，这些标识共同支持跨库检索。
• Because zinc deficiency is common, it has no MONDO or Orphanet entry, while the inherited absorptive form acrodermatitis enteropathica is catalogued separately as a rare disease.由于锌缺乏症常见，它没有 MONDO 或 Orphanet 条目，而遗传性吸收障碍型——肠病性肢端皮炎——则作为罕见病单独收录。
• Clinically the disorder is classified as acute, as seen during zinc-free total parenteral nutrition, or chronic, as seen with inadequate diets and malabsorption, and as severe or marginal according to biochemical and clinical severity.临床上本病分为急性型（见于无锌全肠外营养）与慢性型（见于膳食不足与吸收不良），并按生化及临床严重程度分为重度与边缘性缺乏。
• The English term zinc deficiency has largely replaced older labels such as zinc malnutrition, and Chinese texts use 锌缺乏症, while the distinction from hypozincemia has become central to diagnostic reporting.英文术语「锌缺乏」已基本取代「锌营养不良」等旧称，中文使用「锌缺乏症」，而与低锌血症的区分已成为诊断报告的核心。

History

• In 1869 zinc was first shown to be essential for the growth of the mould Aspergillus niger, which opened the study of zinc as a biological requirement.1869 年首次证明锌是霉菌黑曲霉生长所必需，由此开启了对锌生物学需求的研究。
• In 1929 Lutz measured zinc in human tissues with the dithizone technique and estimated that a 70 kg man contains about 2.2 grams of zinc, and in 1933 zinc was shown to be essential for rat growth.1929 年 Lutz 用双硫腙法测定人体组织锌，估计 70 千克成人含锌约 2.2 克，1933 年又证明锌对大鼠生长必需。
• In 1963 a 21-year-old Iranian man with stunted growth, infantile genitalia and anaemia recovered on zinc supplementation, and three zinc-dependent enzymes were described in the same year.1963 年一名伴生长迟缓、性器官幼稚与贫血的 21 岁伊朗男性在补锌后恢复，同年还描述了三种依赖锌的酶。
• In 1972 fifteen rejected Iranian army inductees with features of zinc deficiency all responded to zinc, and in 1973 the first case of acrodermatitis enteropathica was attributed to severe zinc deficiency.1972 年 15 名因锌缺乏表现被拒征的伊朗新兵全部对补锌有反应，1973 年首例肠病性肢端皮炎被归因于严重锌缺乏。
• In 1974 the National Academy of Sciences declared zinc essential for humans and set a recommended dietary allowance, and in 1978 the Food and Drug Administration required zinc in total parenteral nutrition fluids.1974 年美国国家科学院宣布锌为人体必需元素并制定推荐膳食供给量，1978 年美国食品药品监督管理局要求全肠外营养液必须含锌。
• Phytate was recognised in 1960 as a factor that removes zinc from poultry and swine diets, and Reinhold's work in Iran in the 1970s established that phytate can cause human zinc deficiency, a mechanism now central to global risk estimates.1960 年已认识到植酸会夺走禽畜饲料中的锌，Reinhold 于 1970 年代在伊朗的工作则确立植酸可导致人类锌缺乏，这一机制如今是全球风险评估的核心。
• The intestinal zinc transporter ZIP4 was identified in 2002 as the defective protein in acrodermatitis enteropathica, and by 2014 more than 300 zinc-containing enzymes and over 1,000 zinc-containing transcription factors had been catalogued.2002 年鉴定出肠道锌转运体 ZIP4 是肠病性肢端皮炎的缺陷蛋白，至 2014 年已收录 300 余种含锌酶与 1,000 余种含锌转录因子。

Epidemiology

• Zinc deficiency is estimated to affect about 2.2 billion people, and conservative estimates suggest that one quarter of the world population is at risk because of low dietary zinc intake or poor bioavailability.据估计锌缺乏症影响约 22 亿人，保守估计全球四分之一人口因膳食锌摄入不足或生物利用度差而处于风险之中。
• A 2022 pooled analysis of individual-level survey data found that 56 percent of preschool children and 69 percent of non-pregnant women of reproductive age had at least one micronutrient deficiency, with zinc among the most common.2022 年一项基于个体调查数据的汇总分析发现，56% 的学龄前儿童与 69% 的非妊娠育龄女性至少存在一种微量营养素缺乏，锌是其中最常见者之一。
• Estimates assembled for the Global Burden of Disease suggest that the prevalence of zinc deficiency among children under five fell from about 40 percent in 1990 to about 22 percent in 2020, while the associated disability-adjusted life-year rate fell from 24.9 to 3.9 per 100,000 between 1990 and 2019.全球疾病负担相关估计显示，五岁以下儿童锌缺乏患病率由 1990 年的约 40% 降至 2020 年的约 22%，相关伤残调整生命年率在 1990 至 2019 年间由每 10 万人 24.9 降至 3.9。
• The highest human burden is reported in South Asia, sub-Saharan Africa and parts of Central America, where cereal-based diets, low soil zinc and limited access to animal foods converge.人类负担最高的是南亚、撒哈拉以南非洲及中美洲部分地区，当地以谷物为主的膳食、土壤低锌与动物性食物可及性有限相互叠加。
• Infants and young children, pregnant and lactating women, older adults, people on vegetarian or high-phytate diets, patients with chronic kidney or liver disease, and people who have undergone bariatric surgery are at particular risk.婴幼儿、妊娠与哺乳期女性、老年人、素食或高植酸膳食者、慢性肾病或肝病患者以及接受减重手术者风险尤高。
• Severe deficiency is rare outside acrodermatitis enteropathica and prolonged zinc-free parenteral nutrition, whereas mild or marginal deficiency is common and seldom measured.除肠病性肢端皮炎与长期无锌肠外营养外，重度缺乏少见，而轻度或边缘性缺乏常见却很少被检测。
• Zinc deficiency is not a notifiable disease and is rarely recorded on death certificates, so its mortality contribution is estimated indirectly through diarrhoea, pneumonia and other infectious outcomes.锌缺乏症不是法定报告疾病，也极少记录在死亡证明上，因此其死亡贡献只能通过腹泻、肺炎及其他感染结局间接估计。

Pathophysiology

• Zinc exists in the body almost exclusively as the divalent cation Zn2+ and serves catalytic, structural and regulatory roles in more than 300 enzymes and more than 1,000 transcription factors.体内的锌几乎全部以二价阳离子 Zn2+ 形式存在，在 300 余种酶与 1,000 余种转录因子中发挥催化、结构与调控作用。
• Humans have no dedicated zinc store, so a fall in intake is followed within weeks by reduced plasma zinc, impaired enzyme activity and clinical signs when the deficit is sustained.人体没有专门的锌储存库，摄入下降后数周内即可出现血浆锌降低与酶活性受损，缺乏持续时则出现临床体征。
• Dietary zinc availability is reduced by phytate in whole grains and legumes, by low soil zinc in staple crops and, according to a meta-analysis of 143 studies, by elevated atmospheric carbon dioxide, which lowered the zinc content of wheat, rice, peas and soybeans by 3.3 to 9.3 percent at 550 parts per million.全谷物与豆类中的植酸、主粮作物土壤低锌以及大气二氧化碳升高都会降低膳食锌利用，一项纳入 143 项研究的荟萃分析显示，在 550 百万分之二氧化碳下小麦、水稻、豌豆与大豆的锌含量下降 3.3% 至 9.3%。
• Zinc is absorbed mainly by enterocytes through the apical transporter ZIP4, encoded by SLC39A4, and biallelic loss-of-function variants cause acrodermatitis enteropathica with severe, life-long malabsorption.锌主要由肠上皮细胞通过顶膜转运体 ZIP4（由 SLC39A4 编码）吸收，双等位基因功能丧失变异会导致肠病性肢端皮炎，表现为严重且终生的吸收障碍。
• Zinc deficiency impairs both innate and adaptive immunity, alters cytokine production and increases susceptibility to respiratory and gastrointestinal infection, while inflammation itself redistributes zinc away from plasma.锌缺乏同时损害固有免疫与适应性免疫，改变细胞因子产生并增加呼吸道与胃肠道感染易感性，而炎症本身又使锌从血浆重新分布。
• In the gut, zinc supports enterocyte proliferation, brush-border enzyme activity and tight-junction integrity, so deficiency prolongs diarrhoea and diarrhoea in turn increases faecal zinc loss, creating a self-reinforcing cycle.在肠道，锌支持肠上皮细胞增殖、刷状缘酶活性与紧密连接完整性，因此缺乏会延长腹泻，而腹泻又增加粪便锌丢失，形成自我强化的恶性循环。
• Rapidly turning-over tissues such as skin, hair, nails and testes are especially sensitive, which explains dermatitis, alopecia, nail dystrophy, impaired wound healing and reduced testosterone production.皮肤、毛发、指甲与睾丸等更新迅速的组织尤其敏感，这解释了皮炎、脱发、指甲营养不良、伤口愈合受损与睾酮生成减少。

Clinical features

• The characteristic rash is a dry, scaly, erythematous dermatitis that favours the perioral, perianal and acral areas and may resemble seborrhoeic dermatitis or psoriasis.典型皮疹为干燥、脱屑的红斑性皮炎，好发于口周、肛周与肢端，可类似脂溢性皮炎或银屑病。
• Hair becomes sparse and thin, nails develop ridges, splitting or paronychia, and wound healing is delayed in proportion to the severity of depletion.毛发变得稀疏纤细，指甲出现纵嵴、开裂或甲沟炎，伤口愈合延迟程度与缺乏严重度相称。
• Diarrhoea is both a consequence and a cause of deficiency, and in children it may be acute, persistent or chronic, with increased stool frequency and duration.腹泻既是锌缺乏的后果也是其原因，儿童可表现为急性、持续性或慢性腹泻，排便次数增多、病程延长。
• Oral manifestations include stomatitis, glossitis, angular cheilitis and non-specific ulceration, and severe deficiency can impair taste and smell and cause night blindness, especially when vitamin A is also low.口腔表现包括口炎、舌炎、口角炎与非特异性溃疡，重度缺乏可损害味觉与嗅觉并引起夜盲，尤其在同时缺乏维生素 A 时。
• Immune impairment predisposes to recurrent respiratory, gastrointestinal and skin infections, and pneumonia is a common complication in severely deficient children.免疫功能受损使患者易反复发生呼吸道、胃肠道与皮肤感染，肺炎是重度缺乏儿童的常见并发症。
• In children, deficiency causes growth faltering, delayed bone maturation and delayed puberty, and in adolescents and adults it can produce hypogonadism and reduced libido.儿童缺乏可致生长迟缓、骨成熟延迟与青春期延迟，青少年及成人则可出现性腺功能减退与性欲下降。
• Behavioural and cognitive effects include irritability, lethargy, poor attention, anhedonia and depressed mood, and supplementation has been reported to improve hedonic tone rapidly in deficient individuals.行为与认知方面可表现为易激惹、嗜睡、注意力差、快感缺失与情绪低落，据报道补充锌可使缺乏者的快感体验迅速改善。
• Pregnancy and lactation raise zinc requirements, and severe maternal deficiency has been associated with prolonged labour, haemorrhage, placental abruption and adverse fetal outcomes in case reviews of acrodermatitis enteropathica.妊娠与哺乳提高锌需要量，肠病性肢端皮炎的病例回顾提示严重母体缺乏与产程延长、出血、胎盘早剥及不良胎儿结局相关。

Diagnosis

• Diagnosis begins with clinical suspicion based on dermatitis, diarrhoea, alopecia, poor growth, infection or a diet low in animal protein and high in phytate, together with a careful drug, surgical and absorption history.诊断始于临床怀疑，依据皮炎、腹泻、脱发、生长不良、感染或低动物蛋白高植酸膳食，并结合用药、手术与吸收不良史。
• Serum or plasma zinc below 70 micrograms per decilitre, with a usual reference range of 70 to 120 micrograms per decilitre, is the most widely used biochemical criterion.血清或血浆锌低于 70 微克/分升（通常参考范围 70 至 120 微克/分升）是最常用的生化标准。
• Plasma zinc has poor sensitivity and specificity because it falls only after prolonged or severe depletion and is reduced by inflammation, hypoalbuminaemia, haemolysis, infection and the postprandial state, so samples should be collected fasting and interpreted with caution.血浆锌敏感性与特异性均差，仅在长期或重度耗竭后才下降，并受炎症、低白蛋白血症、溶血、感染与餐后状态影响，因此应空腹采血并谨慎解读。
• Low alkaline phosphatase is a supportive clue because zinc is a cofactor, whereas hair and nail zinc concentrations are not validated for individual diagnosis.碱性磷酸酶降低是有价值的辅助线索，因为锌是其辅因子，而头发与指甲锌浓度尚未被验证可用于个体诊断。
• A clinical response to a therapeutic trial of oral zinc supports the diagnosis when biochemistry is equivocal, and the response should be documented objectively.当生化结果不明确时，口服锌试验性治疗后的临床反应可支持诊断，且该反应应客观记录。
• Acrodermatitis enteropathica is diagnosed from the clinical triad, persistent low zinc and biallelic SLC39A4 variants, and it should be suspected in infants with periorificial dermatitis and diarrhoea who fail to thrive.肠病性肢端皮炎依据临床三联征、持续性低锌与 SLC39A4 双等位基因变异诊断，对伴口周肛周皮炎、腹泻与生长不良的婴儿应高度怀疑。
• The differential diagnosis includes biotin deficiency, essential fatty acid deficiency, kwashiorkor, seborrhoeic dermatitis, psoriasis, acne, candidiasis and other causes of acquired or inherited malabsorption.鉴别诊断包括生物素缺乏、必需脂肪酸缺乏、夸希奥科病、脂溢性皮炎、银屑病、痤疮、念珠菌病以及其他获得性或遗传性吸收不良。

Management

• Oral zinc salts such as zinc gluconate, zinc sulfate or zinc acetate are the treatment of choice, and moderate deficiency is usually corrected with 0.5 to 1 milligram of elemental zinc per kilogram per day in children or 25 to 50 milligrams daily in adults.口服锌盐（葡萄糖酸锌、硫酸锌或醋酸锌）是首选治疗，中度缺乏儿童通常按每日每公斤元素锌 0.5 至 1 毫克补充，成人每日 25 至 50 毫克。
• In acrodermatitis enteropathica, lifelong zinc replacement at 1 to 3 milligrams per kilogram per day is required, with dose adjustment guided by growth, skin lesions and serum zinc.肠病性肢端皮炎需终身补锌，按每日每公斤 1 至 3 毫克给药，并根据生长、皮损与血清锌调整剂量。
• For childhood diarrhoea, WHO recommends 20 milligrams of elemental zinc daily for 10 to 14 days, or 10 milligrams daily for infants under six months, alongside oral rehydration and continued feeding.对于儿童腹泻，世界卫生组织推荐每日元素锌 20 毫克、疗程 10 至 14 天，六月龄以下婴儿每日 10 毫克，同时给予口服补液并继续喂养。
• Underlying causes such as coeliac disease, inflammatory bowel disease, chronic kidney disease, liver disease, bariatric surgery and alcohol misuse must be treated, because zinc alone will not correct ongoing losses.必须治疗乳糜泻、炎症性肠病、慢性肾病、肝病、减重手术与酒精滥用等基础病因，因为单靠补锌无法纠正持续丢失。
• Dietary counselling should emphasise oysters, red meat, poultry, beans, nuts and whole grains while reducing phytate through soaking, fermentation and leavening, and fortification or agronomic biofortification can raise population-level intake.膳食指导应强调牡蛎、红肉、禽肉、豆类、坚果与全谷物，并通过浸泡、发酵与发面减少植酸，食品强化与农艺生物强化可提高人群摄入。
• The Chinese expert consensus on childhood zinc deficiency recommends 0.5 to 1 milligram per kilogram per day for preterm and small-for-gestational-age infants from two weeks of age to six months corrected age, and sets a tolerable upper intake level of 23 milligrams per day for children.中国儿童锌缺乏症专家共识建议早产儿与小于胎龄儿自生后两周起至矫正月龄六个月按每日每公斤 0.5 至 1 毫克补充，并将儿童可耐受最高摄入量定为每日 23 毫克。
• Long-term supplementation above 40 milligrams per day can cause copper deficiency, anaemia, neutropenia and growth delay, so serum copper, iron and zinc should be monitored during prolonged high-dose therapy.长期每日超过 40 毫克的补充可导致铜缺乏、贫血、中性粒细胞减少与生长延迟，因此长期大剂量治疗期间应监测血清铜、铁与锌。
• With early recognition and repletion, skin, gut and immune abnormalities usually resolve within weeks, growth may catch up over months, and severe deficiency in infancy carries a risk of persistent neurodevelopmental delay.早期识别并补足后，皮肤、肠道与免疫异常通常数周内缓解，生长可在数月内追赶，而婴儿期重度缺乏可能遗留持续性神经发育迟缓。

Research and controversies

• The absence of a sensitive and specific biomarker remains the central methodological problem, and candidate approaches include isotope-dilution tracers, urinary zinc excretion, hair and nail zinc, and composite dietary and biochemical indices.缺乏敏感且特异的生物标志物仍是核心方法学难题，候选方案包括同位素稀释示踪、尿锌排泄、头发与指甲锌以及膳食与生化复合指数。
• Modelling of 151 countries predicts that rising atmospheric carbon dioxide could push an additional 175 million people into dietary zinc deficiency, making crop biofortification a climate-adaptation issue as well as a nutrition policy.对 151 个国家的建模预测，大气二氧化碳升高可能使额外 1.75 亿人陷入膳食锌缺乏，使作物生物强化同时成为气候适应与营养政策议题。
• Gut microbiome studies suggest that zinc status shapes enteric bacterial composition and that dysbiosis may modify the diarrhoea-zinc deficiency cycle, but causal human data are limited.肠道微生物组研究提示锌状态塑造肠道细菌组成，菌群失调可能改变腹泻与锌缺乏的恶性循环，但人类因果数据有限。
• Trials of zinc supplementation for pneumonia, COVID-19 and other infections have produced inconsistent results, and current evidence does not support high-dose zinc as a standalone anti-infective treatment.锌补充用于肺炎、COVID-19 及其他感染的试验结果不一致，现有证据不支持将大剂量锌作为单独的抗菌治疗。
• Zinc has been studied as an adjunct in major depression and attention-deficit hyperactivity disorder, but effect sizes are small, samples are heterogeneous and guidelines do not yet recommend it as a primary treatment.锌曾被研究作为重度抑郁与注意缺陷多动障碍的辅助治疗，但效应量小、样本异质，指南尚未将其列为主要治疗。
• In Central Anatolia, zinc fertilisation of deficient soils increased wheat yields six- to eight-fold and improved child nutrition, and the programme was estimated to generate about 100 million US dollars per year in economic benefit, illustrating how agricultural and clinical interventions can converge.在中部安纳托利亚，对缺锌土壤施锌使小麦增产 6 至 8 倍并改善儿童营养，该项目估计每年带来约 1 亿美元经济效益，显示农业与临床干预可以汇合。