鉴于锌缺乏症表现的多样性,疾病风险人群都应考虑本诊断。导致患者处于锌缺乏症风险的疾病包括:吸收不良症、慢性肠胃病(腹部疾病或克罗恩氏病)[1]Singhal N, Alam S, Sherwani R, et al. Serum zinc levels in celiac disease. Indian Pediatr. 2008;45:319-321.http://www.ncbi.nlm.nih.gov/pubmed/18451454?tool=bestpractice.com[4]Goh J, O'Morain CA. Review article: nutrition and adult inflammatory bowel disease. Aliment Pharmacol Ther. 2003;17:307-320.http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2036.2003.01482.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/12562443?tool=bestpractice.com[5]Ojuawo A, Keith L. The serum concentrations of zinc, copper and selenium in children with inflammatory bowel disease. Cent Afr J Med. 2002;48:116-119.http://www.ncbi.nlm.nih.gov/pubmed/14562534?tool=bestpractice.com、肝病、[6]Narkewicz MR, Krebs N, Karrer F, et al. Correction of hypozincemia following liver transplantation in children is associated with reduced urinary zinc loss. Hepatology. 1999;29:830-833.http://www.ncbi.nlm.nih.gov/pubmed/10051486?tool=bestpractice.com[7]Stamoulis I, Kouraklis G, Theocharis S. Zinc and the liver: an active interaction. Dig Dis Sci. 2007;52:1595-1612.http://www.ncbi.nlm.nih.gov/pubmed/17415640?tool=bestpractice.com肾脏疾病、[17]Perrone L, Gialanella G, Giordano V, et al. Impaired zinc metabolic status in children affected by idiopathic nephrotic syndrome. Eur J Pediatr. 1990;149:438-440.http://www.ncbi.nlm.nih.gov/pubmed/2332016?tool=bestpractice.com[12]Kalantar-Zadeh K, Kopple JD. Trace elements and vitamins in maintenance dialysis patients. Adv Ren Replace Ther. 2003;10:170-182.http://www.ncbi.nlm.nih.gov/pubmed/14708071?tool=bestpractice.com[13]Mahajan SK. Zinc in kidney disease. J Am Coll Nutr. 1989;8:296-304.http://www.ncbi.nlm.nih.gov/pubmed/2674256?tool=bestpractice.com糖尿病、[8]Chausmer AB. Zinc, insulin and diabetes. J Am Coll Nutr. 1998;17:109-115.http://www.ncbi.nlm.nih.gov/pubmed/9550453?tool=bestpractice.com[9]Zheng Y, Li XK, Wang Y, et al. The role of zinc, copper and iron in the pathogenesis of diabetes and diabetic complications: therapeutic effects by chelators. Hemoglobin. 2008;32:135-145.http://www.ncbi.nlm.nih.gov/pubmed/18274991?tool=bestpractice.com镰状细胞病、[14]Prasad AS. Zinc deficiency in patients with sickle cell disease. Am J Clin Nutr. 2002;75:181-182.http://ajcn.nutrition.org/content/75/2/181.fullhttp://www.ncbi.nlm.nih.gov/pubmed/11815307?tool=bestpractice.com[11]Bao B, Prasad AS, Beck FW, et al. Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients. Transl Res. 2008;152:67-80.http://www.ncbi.nlm.nih.gov/pubmed/18674741?tool=bestpractice.com、HIV 感染。[15]Koch J, Neal EA, Schlott MJ, et al. Zinc levels and infections in hospitalized patients with AIDS. Nutrition. 1996;12:515-518.http://www.ncbi.nlm.nih.gov/pubmed/8878145?tool=bestpractice.com[16]Kupka R, Fawzi W. Zinc nutrition and HIV infection. Nutr Rev. 2002;60:69-79.http://www.ncbi.nlm.nih.gov/pubmed/11908743?tool=bestpractice.com同理,使用某些药物(如氢氯噻嗪、青霉胺、乙胺丁醇和某些抗生素)进行慢性治疗的患者、酗酒者、[18]Kang YJ, Zhou Z. Zinc prevention and treatment of alcoholic liver disease. Mol Aspects Med. 2005;26:391-404.http://www.ncbi.nlm.nih.gov/pubmed/16099027?tool=bestpractice.com[19]Rico H. Alcohol and bone disease. Alcohol Alcohol. 1990;25:345-352.http://www.ncbi.nlm.nih.gov/pubmed/2222569?tool=bestpractice.com素食者、严格素食者和营养不良的婴儿[20]Hambidge KM, Krebs NF. Zinc deficiency: a special challenge. J Nutr. 2007;137:1101-1105.http://jn.nutrition.org/content/137/4/1101.fullhttp://www.ncbi.nlm.nih.gov/pubmed/17374687?tool=bestpractice.com更易患锌缺乏症。老年人患锌缺乏症会导致其感染易感性和骨质疏松症发病率增加。[21]Haase H, Mocchegiani E, Rink L. Correlation between zinc status and immune function in the elderly. Biogerontology. 2006;7:421-428.http://www.ncbi.nlm.nih.gov/pubmed/16953331?tool=bestpractice.com[10]Atik OS, Uslu MM, Eksioglu F, et al. Etiology of senile osteoporosis: a hypothesis. Clin Orthop Relat Res. 2006;443:25-27.http://www.ncbi.nlm.nih.gov/pubmed/16462422?tool=bestpractice.com某些研究表明补充锌可以减少感染的危险。[26]Prasad AS, Beck FW, Bao B, et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr. 2007;85:837-844.http://ajcn.nutrition.org/content/85/3/837.fullhttp://www.ncbi.nlm.nih.gov/pubmed/17344507?tool=bestpractice.com[65]Vakili R, Vahedian M, Khodaei GH, et al. Effects of zinc supplementation in occurrence and duration of common cold in school aged children during cold season: a double-blind placebo-controlled trial. Iran J Pediatr. 2009;19:376-380.http://www.bioline.org.br/request?pe09044在另一项锌缺乏症高危儿科群体的研究中,锌补充剂可以减少腹泻的发病率。[66]Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2013;(1):CD005436.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005436.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23440801?tool=bestpractice.com发病率改善:有高质量证据表明锌补充剂可以减少锌缺乏症儿科群体的腹泻发病率。[66]Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2013;(1):CD005436.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005436.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23440801?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。
由于在轻微缺乏的情况下,血清锌水平的敏感度相对较低,若症状较为典型,即使检测结果正常,仍应考虑口服补充剂。若患者处于高危状态,应依经验给予补充剂。
由于其他营养元素的缺乏(比如铁和维生素 D)常常与锌缺乏并存,应同时检查这些营养素并在缺乏时补充,因为单独补充锌可能无法得到显著的临床疗效。[67]Mazariegos M, Hambidge KM, Westcott JE, et al. Neither a zinc supplement nor phytate-reduced maize nor their combination enhance growth of 6- to 12-month-old Guatemalan infants. J Nutr. 2010;140:1041-1048.http://jn.nutrition.org/content/140/5/1041.fullhttp://www.ncbi.nlm.nih.gov/pubmed/20335626?tool=bestpractice.com锌补充剂和铁补充剂可以联合或单独使用,尽管有证据显示单独用药对儿童生长迟缓的疗效更佳。[68]Chang S, El AS, Bari S, et al. Supplementing iron and zinc: double blind, randomized evaluation of separate or combined delivery. Eur J Clin Nutr. 2010;64:153-160.http://www.ncbi.nlm.nih.gov/pubmed/19904293?tool=bestpractice.com对于获得性锌缺乏症患者,需致力于改善其疾病诱发条件。肠病性肢端皮炎患者需终生服用锌补充剂。
锌补充剂
建议的每日锌摄入量相对较低,而成人标准口服补充量约为每天 20 到 40 mg。[69]Institute of Medicine (U.S.). Panel on Micronutrients. DRI: Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Chapter 12: zinc. Washington, DC: National Academy Press; 2001:442-501.http://www.nap.edu/read/10026/chapter/14
建议每日锌(基础)摄入量:NIH Office of Dietary Supplements fact sheet for health professionals: zinc
4 岁以下儿童每天 3 mg。
4-8 岁儿童每天 5 mg
9-13 岁儿童每天 8 mg
非妊娠和非泌乳期成年女性每天 9 mg
成年男性每天 11 mg
妊娠期和泌乳期每天 11 到 12 mg。
由营养不良或患有不可逆吸收障碍性疾病(包括克罗恩氏病或短肠综合征)引起的重度缺乏症可能需要紧急补充较高剂量的锌(>50 mg/日)mg。
在>50 mg/日的剂量下,常见恶心、腹部不适和腹泻等肠胃症状,而>150 mg/日的剂量可能会对免疫状态、血脂、铁和铜吸收产生不良影响,并可导致潜在的生殖泌尿系统问题。
当长期补充锌时,尤其是高剂量使用时,监测血浆/血清铜的状态是很有帮助的。在长期补充锌期间或在有记录证明铜缺乏的病例中,可以给予铜补充剂。
补充剂配方包括硫酸锌、醋酸锌、天冬氨酸锌、乳清酸锌和葡萄糖酸锌。典型剂量可以长期安全使用。需监控患者的症状改善情况,并在治疗的 3-6 月后检测血清锌水平。若发现未补足,则锌摄入量需要提高;但应对患者进行毒性监测。需要重点注意的是不同的锌配方的生物利用度差别巨大,如天冬氨酸锌或乳清酸锌比氧化锌更易吸收。
对于肠病性肢端皮炎,患者需要终生服药。若长期补充锌,则可能需要依照连续的血清锌检测来制定个体化剂量。此外,由于在吸收方面锌与铜是竞争关系,应定期对铜水平进行评估,同期铜补充剂的使用有时也是必要的。治疗的中断会导致症状和体征的复发。由于锌缺乏症的皮肤表现与酶功能缺陷相关,局部治疗通常无效。
除了肠衰竭和/或长期接受全肠胃外营养的患者之外,基本没有必要使用肠胃外锌。[70]Sriram K, Lonchyna VA. Micronutrient supplementation in adult nutrition therapy: practical considerations. JPEN J Parenter Enteral Nutr. 2009;33:548-562.http://www.ncbi.nlm.nih.gov/pubmed/19454751?tool=bestpractice.com