科学补碘的基础与应用研究进展

时间:2020-04-07

           本期内容由中国营养学会微量元素分会供稿,与您分享科学补碘的基础与应用研究进展。

 

碘是人体新陈代谢和生长发育必需的微量元素,缺乏与过量均增加甲状腺疾病的风险。我国自实施食盐加碘以来,在防治碘缺乏病方面取得了巨大成就,随着人民生活水平的提升,碘营养安全水平研究不断深入,干预策略逐步优化。

1.不同人群碘安全摄入水平的基础研究

基于碘适宜的需求,国际组织和各国政府均制定了碘的膳食摄入量标准,其最直接有效的证据来自于人体代谢实验和人群流行病调查。有关人体碘代谢研究的数据较少,我国标准的制定缺乏国人的研究数据。因此,确定不同人群碘适宜摄入水平对评价和保证居民碘营养具有重要意义。

1.1成人碘安全摄入水平

最早的碘安全摄入水平数据来自于20世纪80年代,美国Gardner[1]和Paul[2]进行的人体代谢实验。为获得国人的数据,张万起团队在2004年中国营养学会和2008年国家自然基金的支持下,开展了我国碘安全摄入量的成人双盲RCT实验研究[3,4],得到中国居民成人碘安全摄入水平(UL)为600μg/d[5]。与国外经典研究相比,该研究以更多的志愿者(8倍)、更细的剂量分组(4倍)以及更长的观察周期(2倍),获得证据度更高的研究结果,且该研究首次以我国居民作为观察对象,更好地反映国人碘需求,确定国人碘安全水平。

1.2儿童碘安全摄入水平

相比于成人,儿童、孕妇、乳母及婴幼儿对碘摄入水平更为敏感,且难以直接开展人体RCT试验,早期Ingenbleek[6]等分别对1.5-2.5岁的12名蛋白—能量营养不良和7名营养恢复期儿童实施的两项碘平衡实验,为制定儿童的碘参考摄入量标准奠定了基础。我国具有自然水碘分布梯度优势,可以选择长期暴露于不同碘水平的人群作为研究对象开展研究。张万起等对我国自然碘暴露下的大样本儿童开展调查,重复采集24h尿结合膳食评估精确推算儿童碘摄入量水平和甲状腺功能变化情况,结果提示我国7-10岁儿童的碘UL为250μg/d,11-14岁儿童的碘UL为300μg/d[7,8],尿碘超过600μg/L时患亚临床甲减的风险增加[9]。该研究结果是首个直接来自儿童碘摄入量标准研究的大样本人群研究证据。

1.3孕妇碘安全摄入量水平

妊娠期妇女的碘营养不仅影响自身健康更关乎胎儿的生长发育[10-13]。孕妇是碘营养关注的重点人群[14,15]。张万起等对高水碘地区孕妇的研究表明,尿碘浓度大于250μg/L时可出现亚临床甲减的流行;当孕妇膳食碘摄入达到500μg/d左右时可能引起相应的健康危害[16]。随后,滕卫平研究团队基于7190名孕妇的研究同样验证了该结果[17]。并且,研究证明母亲的高碘摄入或自身高碘暴露可增加新生儿TSH升高的危险性[12,18,19]。母亲碘营养水平对胎儿和新生儿生长发育至关重要,尤其是“生命前1000天”[13]。Zimmermann等[20]对配方奶粉喂养婴儿进行的RCT实验结果显示,婴儿EAR为72μg/d。但目前仍缺乏我国纯乳母喂养的哺乳期妇女及婴儿的碘安全水平的相关研究数据,这些领域仍是我们今后工作的重点内容。

2.碘营养状况评价体系

不同人群碘适宜摄入水平的研究需要基于个体碘营养状况的评价。目前有多种指标与碘营养相关,可分为群体和个体碘营养水平的评价指标。群体碘营养评价指标包括人群的尿碘中位数、甲状腺肿大率、新生儿TSH筛查阳性率等;评价个体碘营养的指标包括甲状腺容积、甲状腺功能、24h尿碘排出量、血清碘等。其中,一次性尿碘是常用的评估指标,但由于影响因素多、个体波动较大,具有一定的局限性[21,22],目前使用的尿碘评价标准延用了WHO/UNICEF/IGG基于尿碘中位数提出的人群碘营养状况评价标准[23]。近年来,基于国人数据,尿碘评价人群碘营养状况的有效性也得到了评估[22,24]。此外,基于国人数据的儿童甲状腺体积标准以及血清碘评价效果有了进一步研究进展[25-29]。其他指标,如盐碘含量、合格碘盐食用率[30]、水碘含量[31]、甲状腺球蛋白[32,33]、儿童智商等也能够为评价碘营养状况提供参考[34-36]。碘营养评价体系在不断完善。

新时代背景下,随着公民生活水平的提高和精准医疗政策的实施,个体碘营养评价的需求也在不断增加。互联网结合碘膳食频率问卷为实现个体精准碘营养评价提供了新途径。食物频率问卷可反映调查对象长期膳食的平均化水平,经过碘营养考量优化的碘专用食物频率问卷更快捷,能稳定地评价个体的碘营养状况,其有效性已被国内外研究多次验证[37-40]。膳食评价结合互联网、手机APP应用于个体营养评估的系统正在逐渐完善,有待推广应用[41,42],此评价方式在国际上也被广泛认同[43,44]。相比较于常规碘营养评价方法,基于地域饮食特点和膳食频率问卷构建的“互联网+”个体碘营养状况评价的方式,将节省大量的人力、物力和财力,具有更好的使用前景和应用价值,这也将是新时代个体精准碘营养评价的发展方向。

3.碘摄入量标准应用

随着碘营养水平及碘对人体健康影响研究的不断深入,我国碘营养健康标准体系也在不断完善。2013年修订发布的《中国居民膳食碘参考摄入量》首次基于国人数据对成人碘UL、婴幼儿碘AI和乳母RNI进行了全新的制订[5]。其他人群的碘标准修订参照循证营养学方法和理论,从源头考证,并借鉴了美国、WHO和ICCIDD相关标准的制定方法。近几年,随着研究的深入,新的国人碘膳食摄入数据不断更新完善[3,7-9,45],这为下一次的修订提供了进一步的数据支撑。2017年,国家卫健委颁布了国家卫生行业标准《中国居民膳食营养素参考摄入量第3部分:微量元素》(WS/T578.3-2017),为我国居民科学合理碘营养膳食提供了第一个国家标准。2018年,汇聚地方病、营养、内分泌等领域专家共识的第一部《中国居民补碘指南》发布。这些标准、指南为落实“因地制宜、分类指导、科学补碘”的防治策略提供了有力支撑。

综上,顺应时代发展和公众健康诉求,需要我们不断完善人群碘营养标准数据和监测指标体系,建立公众个体化碘适宜精准评价方法。同时,在综合考虑个体饮食习惯、当地水碘和主要食物碘含量及个体生理特征的基础上,指导公众选择恰当浓度碘盐,真正实现全民碘营养适宜,通过科学补碘积极推进全民健康。

中国营养学会微量元素分会

 

 

参考文献

[1]   Gardner D F, Centor R M, Utiger R D. Effects of low dose oral iodide supplementation on thyroid function in normal men[J]. Clin Endocrinol (Oxf), 1988, 28(3): 283-8.

[2]   Paul T, Meyers B, Witorsch R J, Pino S, Chipkin S, Ingbar S H, Braverman L E. The effect of small increases in dietary iodine on thyroid function in euthyroid subjects[J]. Metabolism, 1988, 37(2): 121-4.

[3]   Sang Z, Wang P P, Yao Z, Shen J, Halfyard B, Tan L, Zhao N, Wu Y, Gao S, Tan J, Liu J, Chen Z, Zhang W. Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial[J]. Am J Clin Nutr, 2012, 95(2): 367-73.

[4]   桑仲娜, 沈钧, 刘嘉玉, 吴蕴棠, 陈祖培, 张万起. 关于成人碘安全摄入量的探讨[J]. 营养学报, 2009, 31(01):15-20.

[5]   张万起. 碘. 中国营养学会. 中国居民膳食营养素参考摄入量 (2013 版).[M].  北京: 科学出版社, 2014,230-237.

[6]   Ingenbleek Y, Malvaux P. Iodine balance studies in protein-calorie malnutrition[J]. Arch Dis Child, 1974, 49(4): 305-9.

[7]   Chen W, Zhang Y, Hao Y, Wang W, Tan L, Bian J, Pearce E N, Zimmermann M B, Shen J, Zhang W. Adverse effects on thyroid of Chinese children exposed to long-term iodine excess: optimal and safe Tolerable Upper Intake Levels of iodine for 7- to 14-y-old children[J]. Am J Clin Nutr, 2018, 107(5): 780-788.

[8]   Chen W, Li X, Wu Y, Bian J, Shen J, Jiang W, Tan L, Wang X, Wang W, Pearce E N, Zimmermann M B, Carriquiry A L, Zhang W. Associations between iodine intake, thyroid volume, and goiter rate in school-aged Chinese children from areas with high iodine drinking water concentrations[J]. Am J Clin Nutr, 2017, 105(1): 228-233.

[9]   Sang Z, Chen W, Shen J, Tan L, Zhao N, Liu H, Wen S, Wei W, Zhang G, Zhang W. Long-term exposure to excessive iodine from water is associated with thyroid dysfunction in children[J]. J Nutr, 2013, 143(12): 2038-43.

[10] Zhang Y, Du C, Wang W, Chen W, Shao P, Wang C, Leng J, Shen J, Tan L, Zhang W. Effect of maternal and neonatal factors on neonatal thyroid stimulating hormone: Results from a population-based prospective cohort study in China[J]. J Trace Elem Med Biol, 2018, 49: 151-156.

[11] Pearce E N, Lazarus J H, Moreno-Reyes R, Zimmermann M B. Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns[J]. Am J Clin Nutr, 2016, 104 Suppl 3: 918s-23s.

[12] Nepal A K, Suwal R, Gautam S, Shah G S, Baral N, Andersson M, Zimmermann M B. Subclinical Hypothyroidism and Elevated Thyroglobulin in Infants with Chronic Excess Iodine Intake[J]. Thyroid, 2015, 25(7): 851-9.

[13] Stinca S, Andersson M, Herter-Aeberli I, Chabaa L, Cherkaoui M, El Ansari N, Aboussad A, Weibel S, Zimmermann M B. Moderate-to-Severe Iodine Deficiency in the "First 1000 Days" Causes More Thyroid Hypofunction in Infants Than in Pregnant or Lactating Women[J]. J Nutr, 2017, 147(4): 589-595.

[14] Hynes K L, Otahal P, Hay I, Burgess J R. Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort[J]. J Clin Endocrinol Metab, 2013, 98(5): 1954-62.

[15] Bath S C, Steer C D, Golding J, Emmett P, Rayman M P. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC)[J]. Lancet, 2013, 382(9889): 331-7.

[16] Sang Z, Wei W, Zhao N, Zhang G, Chen W, Liu H, Shen J, Liu J, Yan Y, Zhang W. Thyroid dysfunction during late gestation is associated with excessive iodine intake in pregnant women[J]. J Clin Endocrinol Metab, 2012, 97(8): E1363-9.

[17] Shi X, Han C, Li C, Mao J, Wang W, Xie X, Li C, Xu B, Meng T, Du J, Zhang S, Gao Z, Zhang X, Fan C, Shan Z, Teng W. Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: a cross-sectional study of 7190 pregnant women in China[J]. J Clin Endocrinol Metab, 2015, 100(4): 1630-8.

[18] Chen W, Sang Z, Tan L, Zhang S, Dong F, Chu Z, Wei W, Zhao N, Zhang G, Yao Z, Shen J, Zhang W. Neonatal thyroid function born to mothers living with long-term excessive iodine intake from drinking water[J]. Clin Endocrinol (Oxf), 2015, 83(3): 399-404.

[19] Nishiyama S, Mikeda T, Okada T, Nakamura K, Kotani T, Hishinuma A. Transient hypothyroidism or persistent hyperthyrotropinemia in neonates born to mothers with excessive iodine intake[J]. Thyroid, 2004, 14(12): 1077-83.

[20] Dold S, Zimmermann M B, Baumgartner J, Davaz T, Galetti V, Braegger C, Andersson M. A dose-response crossover iodine balance study to determine iodine requirements in early infancy[J]. Am J Clin Nutr, 2016, 104(3): 620-8.

[21] Chen W, Wu Y, Lin L, Tan L, Shen J, Pearce E N, Guo X, Wang W, Bian J, Jiang W, Zhang W. 24-Hour Urine Samples Are More Reproducible Than Spot Urine Samples for Evaluation of Iodine Status in School-Age Children[J]. J Nutr, 2016, 146(1): 142-6.

[22] Zhang H, Wu M, Yang L, Wu J, Hu Y, Han J, Gu Y, Li X, Wang H, Ma L, Yang X. Evaluation of median urinary iodine concentration cut-off for defining iodine deficiency in pregnant women after a long term USI in China[J]. Nutr Metab (Lond), 2019, 16: 62.

[23] Who/Uicef/Ign. Assessment of Iodine Deficiency Disorders and Monitoring Their Elimination: A Guide for Programme Managers. Third edition. Available at: https://apps.who.int/iris/bitstream/handle/10665/43781/ 9789241595827_eng.pdf.[J], 2007.

[24] Yang L, Li M, Liu X, Wu M, Zhang J, Zhao L, Ding G, Yang X. Evaluation of Iodine Nutritional Status Among Pregnant Women in China[J]. Thyroid, 2020, 30(3): 443-450.

[25] Chen W, Zhang Q, Wu Y, Wang W, Wang X, Pearce E N, Tan L, Shen J, Zhang W. Shift of Reference Values for Thyroid Volume by Ultrasound in 8- to 13-Year-Olds with Sufficient Iodine Intake in China[J]. Thyroid, 2019, 29(3): 405-411.

[26] Pan Z, Cui T, Chen W, Gao S, Pearce E N, Wang W, Chen Y, Guo W, Tan L, Shen J, Zhang W. Serum iodine concentration in pregnant women and its association with urinary iodine concentration and thyroid function[J]. Clin Endocrinol (Oxf), 2019, 90(5): 711-718.

[27] Cui T, Wang W, Chen W, Pan Z, Gao S, Tan L, Pearce E N, Zimmermann M B, Shen J, Zhang W. Serum Iodine Is Correlated with Iodine Intake and Thyroid Function in School-Age Children from a Sufficient-to-Excessive Iodine Intake Area[J]. J Nutr, 2019, 149(6): 1012-1018.

[28] Liu P, Su X, Li M, Shen H, Yu J, Kelly P J, Meng F, Liu L, Fan L, Li M, Liu S, Sun D. Should urinary iodine concentrations of school-aged children continue to be used as proxy for different populations? Analysis of data from Chinese national surveys[J]. Br J Nutr, 2016, 116(6): 1068-76.

[29] Ji C, Bu Y, Tian C, Fan L, Liu S, Liu Y, Sun D. Determination of Reference Intervals of Ratios of Concentrations of Urinary Iodine to Creatinine and Thyroid Hormone Concentrations in Pregnant Women Consuming Adequate Iodine in Harbin, Heilongjiang Province[J]. Biol Trace Elem Res, 2020, 193(1): 36-43.

[30] Li Y, Teng D, Ba J, Chen B, Du J, He L, Lai X, Teng X, Shi X, Li Y, Chi H, Liao E, Liu C, Liu L, Qin G, Qin Y, Quan H, Shi B, Sun H, Tang X, Tong N, Wang G, Zhang J A, Wang Y, Xue Y, Yan L, Yang J, Yang L, Yao Y, Ye Z, Zhang Q, Zhang L, Zhu J, Zhu M, Ning G, Mu Y, Zhao J, Shan Z, Teng W. Efficacy and Safety of Long-Term Universal Salt Iodization on Thyroid Disorders: Epidemiological Evidence from 31 Provinces of Mainland China[J]. Thyroid, 2020.

[31] Shen H, Liu S, Sun D, Zhang S, Su X, Shen Y, Han H. Geographical distribution of drinking-water with high iodine level and association between high iodine level in drinking-water and goitre: a Chinese national investigation[J]. Br J Nutr, 2011, 106(2): 243-7.

[32] Nazeri P, Shab-Bidar S, Pearce E N, Shariat M. Thyroglobulin Concentration and Maternal Iodine Status During Pregnancy: A Systematic Review and Meta-Analysis[J]. Thyroid, 2020.

[33] Zimmermann M B, Aeberli I, Andersson M, Assey V, Yorg J A, Jooste P, Jukic T, Kartono D, Kusic Z, Pretell E, San Luis T O, Jr., Untoro J, Timmer A. Thyroglobulin is a sensitive measure of both deficient and excess iodine intakes in children and indicates no adverse effects on thyroid function in the UIC range of 100-299 mug/L: a UNICEF/ICCIDD study group report[J]. J Clin Endocrinol Metab, 2013, 98(3): 1271-80.

[34] Ma Z F, Venn B J, Manning P J, Cameron C M, Skeaff S A. The sensitivity and specificity of thyroglobulin concentration using repeated measures of urinary iodine excretion[J]. Eur J Nutr, 2018, 57(4): 1313-1320.

[35] Andersen S, Noahsen P, Westergaard L, Laurberg P. Reliability of thyroglobulin in serum compared with urinary iodine when assessing individual and population iodine nutrition status[J]. Br J Nutr, 2017, 117(3): 441-449.

[36] Sutrisna A, Knowles J, Basuni A, Menon R, Sugihantono A. Iodine Intake Estimation from the Consumption of Instant Noodles, Drinking Water and Household Salt in Indonesia[J]. Nutrients, 2018, 10(3).

[37] Naess S, Aakre I, Kjellevold M, Dahl L, Nerhus I, Midtbo L K, Markhus M W. Validation and reproducibility of a new iodine specific food frequency questionnaire for assessing iodine intake in Norwegian pregnant women[J]. Nutr J, 2019, 18(1): 62.

[38] Wu Y, Chen W, Shen J, Tan L, L'abbe M R, Pearce E N, Wang W, Tian X, Wang W, Zhang W. Reproducible and reliable general semiquantitative food frequency questionnaire for evaluating iodine intake in Chinese children[J]. Nutr Res, 2018, 55: 72-80.

[39] Condo D, Makrides M, Skeaff S, Zhou S J. Development and validation of an iodine-specific FFQ to estimate iodine intake in Australian pregnant women[J]. Br J Nutr, 2015, 113(6): 944-52.

[40] Rasmussen L B, Ovesen L, Bulow I, Jorgensen T, Knudsen N, Laurberg P, Perrild H. Evaluation of a semi-quantitative food frequency questionnaire to estimate iodine intake[J]. Eur J Clin Nutr, 2001, 55(4): 287-92.

[41] 张万起. 解决当前重点人群碘营养问题的关键策略:个体化碘适宜方案[C]. 中国营养学会微量元素营养分会.中国营养学会微量元素营养第十二次学术会议暨第六届微量元素营养分会会员大会论文集.中国营养学会微量元素营养分会:中国营养学会,2014:142-143.

[42] 张万起. 解决当前重点人群碘营养问题的关键策略——基于互联网的公众个体化碘适宜方案[C]. 中国营养学会(CHINESE NUTRITION SOCIETY).第十二届全国营养科学大会论文汇编.中国营养学会(CHINESE NUTRITION SOCIETY):中国营养学会,2015:201.

[43] Cade J E. Measuring diet in the 21st century: use of new technologies[J]. Proc Nutr Soc, 2017, 76(3): 276-282.

[44] Carter M C, Albar S A, Morris M A, Mulla U Z, Hancock N, Evans C E, Alwan N A, Greenwood D C, Hardie L J, Frost G S, Wark P A, Cade J E. Development of a UK Online 24-h Dietary Assessment Tool: myfood24[J]. Nutrients, 2015, 7(6): 4016-32.

 

[45] Tan L, Tian X, Wang W, Guo X, Sang Z, Li X, Zhang P, Sun Y, Tang C, Xu Z, Shen J, Zhang W. Exploration of the appropriate recommended nutrient intake of iodine in healthy Chinese women: an iodine balance experiment[J]. Br J Nutr, 2018: 1-31.

 

注:转自中国营养学会


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