1. 无麸质饮食的理论基础与科学验证分歧
1.1 医学背景下的无麸质饮食起源
无麸质饮食（Gluten-Free Diet, GFD）并非近代才出现的健康趋势，其最初的理论基础和临床应用源于对几种特定疾病的治疗需求。这些疾病的核心特征在于患者对麸质（Gluten）——一种存在于小麦、大麦和黑麦等谷物中的蛋白质混合物——产生异常的免疫反应或敏感性 1。
其中，乳糜泻（Celiac Disease, CD）是研究最深入、病理机制最明确的麸质相关疾病。乳糜泻是一种慢性炎症性肠病，由麸质在具有遗传易感性个体（携带HLA-DQ2/HLA-DQ8基因型）体内引发 2。麸质中的特定肽段对人体胃肠道蛋白酶具有高度抵抗性，导致其在肠道内形成致病性肽，进而引发遗传易感人群的自身免疫反应 1。这种反应会损害小肠黏膜，导致绒毛萎缩、隐窝增生以及淋巴细胞浸润，进而引起营养吸收不良及一系列胃肠道和肠外症状 34。乳糜泻的诊断通常依赖于血清自身抗体（如抗转谷氨酰胺酶抗体和抗子宫内膜抗体IgA）和十二指肠活检结果 4。由于其自身免疫性质和对肠道黏膜的持续损害，严格且终身坚持无麸质饮食是目前乳糜泻唯一有效且被广泛认可的治疗方法，旨在阻断对麸质肽的免疫反应，促进肠道修复 45。
除了乳糜泻，非乳糜泻麸质敏感（Non-Celiac Gluten Sensitivity, NCGS）是另一种日益受到关注的麸质相关疾病。NCGS患者在摄入麸质后会出现肠道（如腹痛、腹胀）和肠外症状（如疲劳、头痛、脑雾、皮疹），但其体内不表现出乳糜泻的自身免疫标志物或小肠黏膜的典型损伤，也排除了小麦过敏的可能性 678。NCGS的病理机制尚未完全阐明，可能涉及先天免疫系统的激活、麸质的直接细胞毒性作用，或与其他小麦成分（如FODMAPs、淀粉酶-胰蛋白酶抑制剂）的协同作用 6910。由于缺乏明确的生物标志物，NCGS的诊断主要基于症状对无麸质饮食的反应以及麸质激发试验 7810。虽然其确切的病理生理过程仍在研究中，但避免麸质摄入通常能显著改善NCGS患者的症状，因此无麸质饮食也被视为这类患者的重要管理手段 11。
此外，小麦过敏（Wheat Allergy, WA）也是麸质相关疾病谱系中的一员，但其机制与乳糜泻和NCGS不同，属于IgE介导的速发型过敏反应 12。患者在摄入小麦后可能出现荨麻疹、呼吸困难甚至过敏性休克等症状。对于小麦过敏患者，避免小麦及其麸质是预防过敏反应的关键。
综上所述，无麸质饮食作为一种临床干预手段，最初是基于对乳糜泻、非乳糜泻麸质敏感和小麦过敏等疾病的深入理解和治疗需求而提出的。它对于这些特定患者群体而言，是维持健康、改善症状乃至预防并发症的必要治疗方式 13。
1.2 非疾病人群干预研究的矛盾结论
尽管无麸质饮食在治疗麸质相关疾病方面具有明确的医学依据，但近年来，在非疾病人群中推行无麸质饮食的健康宣称日益增多，引发了广泛的科学争议。针对健康个体或非麸质敏感人群，大量研究试图探究无麸质饮食对其代谢、肠道菌群以及整体健康的影响，但得出的结论往往存在矛盾和不一致性。
一方面，部分研究表明，对于健康个体而言，短期无麸质饮食可能带来某些积极变化，但其全面健康益处尚未得到充分证实。例如，一项针对健康志愿者进行的短期（四周）干预研究发现，无麸质饮食可导致白细胞计数和C反应蛋白水平降低，并伴有炎症生物标志物的减少趋势，提示其可能具有一定的抗炎作用，尽管对心血管健康的整体改善和生活质量的提升并未观察到显著效果 14。然而，这些发现通常是初步的，且研究周期较短，难以推断长期影响。
另一方面，越来越多的证据指出，非医学指征的无麸质饮食不仅可能缺乏益处，反而可能带来潜在的健康风险。最主要的担忧之一是其对肠道菌群结构和功能的影响。麸质来源的全谷物是膳食纤维的重要来源，而膳食纤维对于维持健康的肠道菌群至关重要。长期无麸质饮食可能影响肠道微生态的平衡，进而对宿主健康产生负面影响 1516。这种改变可能并非一概而论，不同人群的肠道菌群对无麸质饮食的反应可能存在个体差异 16。此外，有研究指出，无麸质饮食的依从性及其对肠道菌群的调节作用不能简单地从一个群体推断到另一个群体，因为个体的肠道微生物组成和代谢活动模式高度个体化，且受多种因素影响 16。
除了对肠道菌群的影响，非医学指征的无麸质饮食还可能导致营养素摄入不均衡。无麸质产品往往以精制淀粉和/或精制面粉为基础，导致其膳食纤维含量较低，且可能缺乏B族维生素、铁、锌、镁和钙等多种微量营养素 1718。一项研究比较了美国市场的39种无麸质产品及其含麸质的同类产品，结果发现无麸质产品平均而言蛋白质含量显著更低，而糖和卡路里含量更高 19。长期摄入此类产品，可能增加营养缺乏的风险 1718。例如，在乳糜泻患者中，尽管无麸质饮食是必需的治疗手段，但仍需警惕营养不均衡问题，特别是膳食纤维的缺乏 17。
此外，一些研究甚至提示了无麸质饮食可能带来的其他健康风险。例如，一项孟德尔随机化研究发现，无麸质饮食与骨质疏松症的发生风险显著相关，提示其可能促进骨质疏松的发生，这与乳糜泻并发症的治疗原则相矛盾，因此提出三者之间存在一种新的关联 20。另一项针对桥本甲状腺炎患者的试验性研究也显示，无麸质饮食并未显著影响氧化应激标志物和甲状腺功能参数，而地中海饮食则表现出更显著的保护作用 21。
综上所述，当前关于非疾病人群无麸质饮食益处的研究结论存在明显矛盾。虽然少数研究提示了潜在的短期抗炎效果，但缺乏强有力的证据支持其对整体健康的长期益处，反而引发了对肠道菌群失衡、营养素缺乏以及其他潜在健康风险的担忧。这种不一致性凸显了在向健康人群推广无麸质饮食时，需要更加谨慎和全面的科学评估。
2. 健康宣称的夸大与证据缺失争议
2.1 营销语境下的功能宣称泛化
在全球健康饮食潮流中，无麸质饮食已超越了其最初的医学治疗范畴，在商业营销的推动下被赋予了多种“健康光环”。各类无麸质产品和饮食方案在宣传中常声称能带来“抗炎”、“提升认知”、“减肥”、“改善消化”乃至“增加活力”等广泛益处。然而，仔细审视这些宣称，会发现其中多数缺乏坚实的科学证据支持，尤其是在非医学必需人群中。
“减肥”宣称： 减肥是无麸质饮食最常见的商业宣称之一。许多宣传材料暗示无麸质饮食能帮助消费者减轻体重，甚至将其包装成一种有效的减肥策略。然而，多项研究和综述指出，目前没有已发表的实验证据支持无麸质饮食能导致体重减轻，或建议普通人群通过避免麸质来减肥 2223。事实上，许多无麸质替代品为了弥补口感和质地，往往会增加糖、脂肪和精制淀粉的含量，导致其热量可能高于传统含麸质产品，长期食用反而可能导致体重增加或营养失衡。例如，一项研究指出，无麸质饮食的依从性往往伴随着更高的血糖指数摄入，可能对体重管理产生负面影响。
“抗炎”宣称： 一些营销宣传将无麸质饮食与“抗炎”效果挂钩，声称通过去除麸质可以减少全身炎症。在乳糜泻患者中，严格的无麸质饮食确实可以显著降低炎症标志物并修复受损肠道，因为麸质是这些患者炎症的直接诱因。然而，对于健康人群，麸质本身并非炎症诱因。虽然有少数短期研究发现无麸质饮食可能降低某些炎症生物标志物，但这并非普遍现象，且其临床意义尚不明确。这些发现不能简单推广到所有个体，尤其是当膳食结构改变可能导致其他营养素（如膳食纤维）摄入不足时，反而可能引发新的健康问题。
“提升认知”和“改善脑雾”宣称： 随着“脑雾”（brain fog）概念的流行，一些无麸质饮食的推广者将其与改善认知功能、提高注意力和清晰思维联系起来。确实，在乳糜泻患者中，存在由麸质引起的认知障碍，即所谓的“脑雾”现象，表现为记忆、注意力和执行功能受损，并且这些症状在坚持无麸质饮食后会有所改善 24。然而，这特指乳糜泻患者的病理生理反应。对于非麸质敏感的健康人而言，没有确凿证据表明无麸质饮食能够普遍提升认知能力或解决非特定原因导致的“脑雾”问题。一些研究甚至发现，自我报告的认知提升可能更多来源于安慰剂效应或对饮食改变的心理期待。
“改善自闭症症状”宣称： 尽管争议较大，但无麸质和无酪蛋白饮食（Gluten-Free and Casein-Free, GFCF diet）在自闭症谱系障碍（ASD）儿童治疗中的应用也曾被广泛讨论。部分研究和家长报告称，GFCF饮食可能有助于缓解ASD儿童的刻板行为和改善认知 2526。然而，这些研究往往样本量小，存在方法学缺陷，且结论不一致 27。一项系统综述指出，尽管有研究表明GFCF饮食可能对ASD核心症状有统计学意义上的改善，但其证据质量有限，需要更大规模、设计更严谨的随机对照试验来验证 2526。目前，主流医学界并未将GFCF饮食作为ASD的常规或推荐治疗方法。
总而言之，商业营销语境下无麸质饮食的健康宣称往往脱离了其医学适应症，过度泛化了少数研究的初步发现或特定疾病患者的治疗效果。这些宣称多数缺乏大规模、高质量随机对照试验的支持，未能提供充分的证据表明无麸质饮食对健康人群具有显著或普遍的健康益处。这种夸大其词的宣传，不仅可能误导消费者，还可能掩盖潜在的营养风险。
2.2 专家共识与公众认知的断层
无麸质饮食在公众中的盛行，与专业医疗机构和权威组织所持的谨慎态度形成了鲜明对比，凸显了信息传播中的严重失真现象。医学专家和营养学界普遍强调无麸质饮食的临床适用性，并对其在健康人群中的盲目推广表示担忧。
权威机构的立场：
世界胃肠病组织（WGO）在其全球指南中明确指出，无麸质饮食是乳糜泻患者唯一的治疗方法。对于非乳糜泻麸质敏感（NCGS）患者，虽然无麸质饮食可能有助于缓解症状，但其诊断和管理仍需在医生指导下进行，并且强调NCGS并非永久性的麸质不耐受，部分患者可能在症状缓解后重新引入少量麸质。美国胃肠病学会（AGA）和欧洲儿科胃肠病学、肝病学和营养学会（ESPGHAN）也发布了类似的立场文件，强调无麸质饮食仅适用于明确诊断的麸质相关疾病患者，特别是乳糜泻患者，其终身严格 adherence 对疾病管理至关重要 28。这些专业机构基于大量临床证据和研究，审慎评估了无麸质饮食的必要性、有效性及潜在风险，其核心观点在于“有病方需，无病无益”。他们担忧，健康人群若非必要地采用无麸质饮食，可能导致营养不均衡（如膳食纤维、B族维生素、铁等微量元素缺乏），甚至增加经济负担，因为无麸质产品往往价格更高。
社交媒体与健康博主的激进推荐：
与权威机构的审慎态度形成鲜明对比的是，社交媒体平台和健康博主对无麸质饮食的激进推荐。在Instagram、TikTok、小红书等平台上，充斥着大量由非专业人士（包括所谓的“健康达人”、“生活方式博主”甚至患者本人）发布的无麸质饮食内容。这些内容往往以个人经验、未经证实的轶事证据或片面的研究结果为支撑，将无麸质饮食描绘成一种“包治百病”的健康万能药。例如，在针对银屑病患者的饮食管理信息分析中，发现Instagram上绝大多数（99%）的饮食相关帖子质量低下，且大部分内容是由患有银屑病的人士发布，而非合格的营养专业人士或医疗保健专业人士，其中“排除性饮食”是最常见的建议，包括无麸质饮食 29。
这些激进推荐常采用以下策略：
- 过度简化复杂问题： 将复杂的代谢和免疫反应简化为“麸质有害论”，宣称麸质是导致炎症、疲劳、体重增加、甚至自闭症等多种非特异性症状的元凶。
- 案例分享替代科学证据： 强调个人实践无麸质饮食后“症状神奇消失”、“精力充沛”、“皮肤改善”等个案，以此吸引并说服追随者，但这些经验缺乏对照组和严格的科学验证。
- 模糊疾病与健康界限： 不区分乳糜泻、NCGS患者的特殊需求与健康人群的日常饮食，模糊了无麸质饮食的适用边界。
- 利用健康焦虑： 迎合现代人对健康、美容、减肥的普遍焦虑，将无麸质饮食包装成实现这些目标的捷径。
- 商业利益驱动： 部分博主或平台可能与无麸质产品品牌存在合作关系，通过推广无麸质饮食来间接促进产品销售。
信息传播中的失真现象：
这种专家共识与公众认知之间的断层，反映了信息传播中的严重失真。权威机构的科学严谨性使得其信息传播相对滞后且难以大众化理解，而社交媒体则以其即时性、互动性和碎片化特点迅速捕获公众注意力。当科学信息被过滤、简化甚至扭曲后，未经证实的健康宣称便更容易泛滥。公众在缺乏专业知识的情况下，往往难以辨别信息的真伪，更倾向于相信那些听起来“有效”且“简单易行”的解决方案，从而盲目跟风，采纳了不必要的无麸质饮食。这种信息不对称不仅浪费了社会资源，也可能对个体健康造成潜在风险。
3. 特殊人群与普通人群的适用性边界争议
3.1 临床确诊患者的必要性与执行难点
对于临床确诊的麸质相关疾病患者，特别是乳糜泻（CD）患者而言，严格无麸质饮食（GFD）并非一种选择，而是不可或缺的医疗干预手段。这种饮食方案的必要性源于其在阻断疾病进展、促进肠道黏膜愈合、改善营养吸收以及预防并发症方面的独特作用。
医学必要性：
乳糜泻是一种自身免疫性疾病，麸质的摄入会持续损伤小肠黏膜，导致绒毛萎缩、隐窝增生和炎症细胞浸润，进而引起营养吸收不良及多种临床症状。严格遵守无麸质饮食是唯一能有效阻止这种免疫反应、修复小肠损伤的方法 3031。长期不遵守或不严格遵守无麸质饮食，不仅会导致症状持续，还可能增加患骨质疏松、不孕不育、神经系统疾病以及某些恶性肿瘤（如小肠淋巴瘤）的风险 3132。因此，对于乳糜泻患者，无麸质饮食是终身且严格的治疗方案，其重要性不亚于药物治疗。通过严格的无麸质饮食，患者的肠道黏膜得以恢复，多数营养缺乏症会得到改善，从而显著提高生活质量 323334。
执行难点：
尽管无麸质饮食对乳糜泻患者至关重要，但在日常生活中严格执行却面临诸多挑战：
- 交叉污染风险： 麸质存在于多种谷物及其加工产品中，即使微量的麸质也可能引发乳糜泻患者的免疫反应。在食品生产、储存、烹饪和餐饮服务过程中，交叉污染是普遍存在的风险。例如，餐馆中用于处理含麸质食物的砧板、餐具或油锅，都可能导致无麸质食物被污染。即便被标记为“无麸质”的产品，也可能因生产线共享等原因存在微量麸质残留，这给患者带来了极大的不确定性 35。
- 替代食品的营养均衡问题： 为了弥补传统含麸质食物（如面包、面食）的缺失，市场涌现出大量无麸质替代品。然而，这些产品往往以精制淀粉（如玉米淀粉、木薯淀粉）为主要原料，口感和营养价值可能不如传统全谷物。研究显示，无麸质产品通常膳食纤维含量较低，并且可能缺乏B族维生素（如叶酸、维生素B12）、铁、锌、镁和钙等重要微量元素 173637。这使得患者在选择替代品时，需要格外关注其营养成分，以避免长期营养不良 38。例如，有研究发现，无麸质饮食患者钙（38% DRI）、维生素D（29% DRI）、维生素C（86% DRI）和叶酸（51% DRI）的摄入量通常低于推荐值 3639。特别是在监狱等特殊受限环境下，无麸质饮食的营养供给挑战更为突出 36。
- 高昂的成本： 无麸质食品的生产成本通常高于普通食品，这直接反映在零售价格上。无麸质面包、饼干、意大利面等替代品往往比同类含麸质产品贵数倍，这给患者带来了额外的经济负担 3040。
- 社会和心理障碍： 严格的无麸质饮食对患者的社交生活造成困扰。聚餐、外出就餐、旅行等场景都可能成为挑战。患者可能因为饮食限制而感到被孤立，或因担心食物不安全而拒绝参加社交活动，从而产生焦虑、压抑等心理问题 4142。此外，患者需要不断学习和掌握复杂的食品标签知识，并主动向他人解释其饮食需求，这本身就是一种心理负担。
- 营养教育与依从性： 尽管许多患者知道无麸质饮食的重要性，但缺乏专业的营养指导和持续的教育可能导致依从性不足。患者可能不清楚哪些食物天然无麸质，哪些含有隐藏麸质，或如何搭配食物以确保营养均衡。长期的饮食限制也容易让人产生厌倦感，影响依从性。研究显示，即使是确诊的乳糜泻患者，仍有部分人存在持续性缺铁性贫血，这可能与微量麸质摄入或小肠吸收功能未完全恢复有关 43。
综上所述，对于临床确诊的麸质相关疾病患者，特别是乳糜泻患者，无麸质饮食是治疗的基石。然而，其执行过程中的交叉污染风险、营养均衡挑战、高昂成本以及社会心理压力，都要求患者、家庭和社会给予更多的支持和理解，并需要专业的营养师和医生进行长期管理和指导。
3.2 健康人群盲目跟随的潜在风险
在健康人群中，无麸质饮食常被视为一种“更健康”的选择，但这种盲目跟随可能带来一系列潜在的营养风险和健康问题，尤其是在长期坚持的情况下。
营养缺乏风险：
无麸质谷物（如大米、玉米、藜麦、荞麦、苋菜籽、小米、高粱等）虽然自身不含麸质，且其中一些（如藜麦）营养价值丰富 44，但当健康人群为了遵循无麸质饮食而刻意避免传统全谷物（如全麦、大麦、黑麦）时，他们的膳食结构可能发生改变，导致关键营养素摄入不足。
- 膳食纤维： 传统全谷物是膳食纤维的重要来源。膳食纤维有助于肠道健康、维持血糖稳定和预防便秘。无麸质饮食往往因排除了富含纤维的麦类谷物，而其替代品（如由精制米粉、玉米淀粉制成的无麸质面包和糕点）的膳食纤维含量通常较低 1734。例如，一项针对乳糜泻患者的长期研究发现，无麸质饮食的膳食纤维摄入量显著低于健康对照组 33。长期膳食纤维摄入不足不仅会影响肠道蠕动，还可能改变肠道菌群结构，降低有益菌群的丰度，甚至导致便秘加重，对于本身肠道功能正常的人群，这种改变可能适得其反 45。
- B族维生素： 小麦、大麦和黑麦是B族维生素（如硫胺素、核黄素、烟酸和叶酸）的重要来源。许多谷物产品还会进行B族维生素强化。当健康人群盲目采用无麸质饮食时，如果未能通过其他食物来源充分补充，可能面临B族维生素缺乏的风险 1734。B族维生素在能量代谢、神经功能和红细胞形成中发挥关键作用，其缺乏可能导致疲劳、贫血和神经系统问题。
- 矿物质： 麸质谷物同样是铁、锌、镁和钙等矿物质的重要膳食来源。无麸质替代产品，尤其是那些未经强化的产品，可能在这些矿物质含量上有所不足 1737。例如，在波兰监狱的一项研究中，无麸质饮食组的钙、叶酸、铁和锌的平均摄入量低于常规饮食组 36。长期缺乏这些矿物质可能对骨骼健康、免疫功能和能量水平产生负面影响。一项对乳糜泻患者的研究显示，无麸质饮食可能增加骨质疏松的风险，这提示了营养不均衡对骨骼健康的潜在影响 31。
- 其他微量营养素： 除了上述营养素，无麸质饮食还可能导致维生素D、磷等其他微量元素的摄入不足 1736。
对肠道菌群的影响：
健康人群的肠道菌群对维持整体健康至关重要。膳食纤维作为益生元，是肠道有益菌的“食物”。长期无麸质饮食，特别是当其伴随着膳食纤维摄入量下降时，可能会导致肠道菌群失衡。一项对健康成年人的初步研究发现，短期无麸质饮食（一个月）后，肠道内有益菌（如双歧杆菌）数量减少，而某些可能与疾病相关的“不健康”细菌数量增加，同时多糖的摄入量也有所下降 45。这种菌群结构的变化可能影响肠道屏障功能、免疫调节和短链脂肪酸的产生，长远来看可能增加炎症风险，甚至与代谢综合征等慢性疾病的发生发展相关。
流行病学数据：
尽管缺乏大规模、长期针对健康人群无麸质饮食影响的流行病学数据，但从乳糜泻患者的经验和有限的健康人群研究中，可以推断出潜在的风险。乳糜泻患者即便严格遵守无麸质饮食，仍需定期监测营养状况，以避免上述营养缺乏。这表明，对于一个原本没有麸质不耐受问题的健康个体而言，盲目地将麸质从饮食中剔除，反而可能打乱其原有的营养平衡，增加健康风险。
总而言之，对于非麸质敏感的健康人群而言，无麸质饮食并非“更健康”的选择，反倒可能因膳食结构单一、缺乏营养知识，或过度依赖加工的无麸质替代品，导致膳食纤维、B族维生素、铁、钙等重要营养素的摄入不足，并可能对肠道菌群产生负面影响。因此，健康人群在考虑无麸质饮食前，应咨询专业医生或营养师，而非盲目跟风。
4. 商业推广与消费市场的互动争议
4.1 无麸质产品市场的扩张逻辑
在过去的十年间，无麸质产品市场经历了显著的扩张，成为全球食品工业中增长最快的细分市场之一。这种扩张并非偶然，而是由多重因素共同驱动，包括资本的积极介入、消费者日益增长的健康焦虑，以及餐饮行业的创新响应。
市场规模与增长数据：
全球无麸质食品市场展现出强劲的增长势头。据估计，从2020年到2027年，无麸质产品市场将以每年约7.6%的复合年增长率（CAGR）持续增长 46。另有报告指出，无麸质食品市场正以惊人的速度增长，预计到2027年，全球市场价值将达到约97亿美元。这一数据不仅反映了市场对无麸质产品的巨大需求，也预示了其在未来一段时间内的持续繁荣。例如，一些分析机构甚至预测，到2027年，全球无麸质食品市场规模将突破100亿美元大关。这种爆发式增长吸引了大量投资者和食品企业的关注。
资本推动：
逐利的资本是推动无麸质市场扩张的重要力量。食品巨头和初创企业纷纷投入研发和生产无麸质产品线，以满足不断扩大的市场需求。风险投资和私募股权基金也看准这一趋势，向无麸质食品品牌注资，助推其产能扩张、渠道建设和市场营销。例如，一些专注于健康食品的投资公司积极寻求无麸质领域的投资机会，通过收购或合作，将其技术和市场优势迅速复制到无麸质领域。这种资本的涌入，使得无麸质产品的种类日益丰富，从传统的面包、意面，延伸到饼干、零食、酱料乃至啤酒等多元化品类，极大地提升了产品的可及性和市场渗透率。
消费者健康焦虑：
日益普遍的健康焦虑是无麸质市场扩张的深层社会动因。随着互联网和社交媒体的普及，消费者能够接触到海量的健康信息，其中不乏对麸质的负面解读，例如将其与肠道问题、炎症反应、疲劳甚至自身免疫疾病联系起来。尽管许多宣称缺乏充分的科学依据，但“避免麸质更健康”的观念在部分消费者心中根深蒂固。这种对未知风险的规避心理，促使许多消费者主动尝试无麸质饮食，即便他们并未被诊断出麸质相关疾病。尤其是那些追求“清洁饮食”、“天然食品”的消费者，更容易被无麸质产品的“健康光环”所吸引。此外，许多人也抱着“宁可信其有，不可信其无”的态度，将无麸质饮食作为一种预防性措施，希望通过改变饮食习惯来改善身体状况或预防潜在疾病。
餐饮行业创新：
餐饮行业的积极响应也为无麸质市场的扩张添砖加瓦。为了迎合消费者的需求，越来越多的餐厅、咖啡馆和烘焙坊开始提供无麸质选项。从专门的无麸质餐厅，到主流餐厅菜单上的“无麸质”标识，这不仅提升了无麸质饮食的便利性，也进一步巩固了其在主流消费市场中的地位。厨师们也积极探索无麸质食材（如木薯淀粉、玉米淀粉、豆类粉、藜麦粉等）在烹饪中的应用，不断推出创新菜品，改善无麸质食品的口感和风味，使其更具吸引力。例如，脉冲豆类（如普通豆、鹰嘴豆、小扁豆和豌豆）因其高蛋白质和纤维含量，以及丰富的生物活性化合物，被广泛研究作为开发无麸质食品的替代品，并被证明在营养和健康益处方面优于许多传统面粉产品 46。这种创新不仅满足了对无麸质食物有医疗需求的患者，也吸引了追求新颖和健康饮食体验的普通消费者。这种消费者需求与餐饮行业供给的良性互动，共同推动了无麸质市场的蓬勃发展。
4.2 标准缺失与标识混乱的乱象
随着无麸质市场的迅速膨胀，全球范围内对“无麸质”产品的定义、标签规范以及监管的滞后，逐渐暴露出诸多乱象，给消费者，特别是麸质敏感人群，带来了困惑甚至健康风险。不同国家和地区对“无麸质”的定义标准存在差异，加之市场监管不力，导致产品标识混乱，消费纠纷频发。
“无麸质”定义标准差异：
目前，国际上对“无麸质”产品最普遍接受的标准是其麸质含量不超过20 ppm（parts per million，百万分之二十）。这一标准被联合国食品法典委员会（Codex Alimentarius Commission）以及欧盟、美国、加拿大等主要经济体采纳。
- 欧盟标准： 欧盟法规（Regulation (EU) No 828/2014）规定，“无麸质”食品的麸质含量必须低于20 mg/kg（即20 ppm）。此外，欧盟还设有“超低麸质”（very low gluten）类别，其麸质含量需低于100 mg/kg，但这个标签在实际市场中应用较少，且易引起混淆。
- 美国标准： 美国食品药品监督管理局（FDA）在2013年发布了无麸质食品标签最终规则，同样将“无麸质”定义为产品中麸质含量不超过20 ppm。
- 其他国家： 许多国家也效仿欧盟和美国的标准。然而，并非所有国家都建立了强制性的无麸质标签标准，一些地区可能仅有推荐性指南，甚至缺乏明确的定义。这种标准的缺失或不统一，导致跨国贸易中无麸质产品的合规性问题。
标识混乱与消费纠纷案例：
尽管有国际标准的存在，但在实际市场操作中，产品标识的混乱现象依然普遍，尤其是在那些监管不完善或消费者意识薄弱的地区。
- 误导性标签： 许多产品可能自然不含麸质（例如米、玉米、豆类），但却刻意突出“无麸质”标签，以迎合市场趋势并获取溢价。虽然这本身不违法，但可能误导消费者认为其比同类天然无麸质产品更健康或更特殊。
- 交叉污染风险未明确： 部分生产商可能在同一生产线上生产含麸质和无麸质产品，但未在标签上明确提示交叉污染风险。这对于对麸质高度敏感的乳糜泻患者来说是极大的隐患。例如，印度一项研究发现，该国市场上10.1%的无麸质产品（包括有标签和无标签的）麸质含量超过20 ppm的规定限值，其中谷物及其产品（面粉、粗粮、意大利面/通心粉、零食）和烘焙食品是受污染最常见的类型 47。这一数据凸显了在一些国家，即便有“无麸质”标识，产品也可能不符合国际标准，对患者构成健康威胁。
- 含燕麦产品的争议： 燕麦本身不含麸质，但由于其种植、收割、运输和加工过程中极易与小麦、大麦等含麸质谷物发生交叉污染，导致市场上多数燕麦产品含有可检测到的麸质。因此，对于乳糜泻患者而言，通常只推荐食用明确标记为“纯燕麦”（pure oats）或“无麸质燕麦”的产品，即这些燕麦在整个供应链中都经过严格控制，确保麸质含量在安全阈值以下。然而，由于监管标准和检测能力的差异，一些“无麸质燕麦”产品仍可能引发争议。例如，加拿大的研究就曾指出，市场上常规燕麦产品普遍存在麸质污染问题，高达88%的燕麦样品麸质含量超过20 mg/kg 48。即便有“纯”燕麦产品被认为是安全的，但也有研究表明某些燕麦品种本身可能引起敏感个体免疫反应 4950。这种复杂性导致消费者在选择含燕麦的无麸质产品时，面临极大的不确定性。
- “天然无麸质”与“认证无麸质”的混淆： “天然无麸质”（naturally gluten-free）指的是某些食材本身就不含麸质，如肉、蛋、鱼、蔬菜、水果和豆类。而“认证无麸质”（certified gluten-free）则意味着产品经过第三方机构的检测和认证，确保其麸质含量符合特定标准。然而，在市场宣传中，这两者常常被混淆，导致消费者误以为所有标有“无麸质”的产品都经过了严格的生产控制和检测。
这些标识混乱和标准差异不仅削弱了消费者对“无麸质”标签的信任，也增加了麸质敏感人群在选择食品时的难度和风险。监管机构需要加强对无麸质产品标识的审查和抽检，统一和完善相关标准，以保障消费者的知情权和健康安全。
5. 长期影响的不确定性与研究呼吁
5.1 现有研究的时间维度局限
当前对无麸质饮食（GFD）影响的科学研究，尤其是在非乳糜泻患者和健康人群中的研究，普遍存在时间维度上的局限性，这成为评估其长期健康效应的一大障碍。绝大多数已发表的研究设计为短期观察或干预，通常持续数周至一年，缺乏对更长时间尺度（如5-10年甚至更长）内健康指标变化的追踪数据。
这种短期研究的特性，使得我们难以全面把握无麸质饮食对人体生理、特别是复杂系统（如肠道微生态和代谢状况）的长期累积效应。例如：
- 肠道微生态的动态变化： 肠道菌群是一个高度复杂的生态系统，其组成和功能受饮食、生活方式等多方面因素的长期影响。短期研究可能捕捉到无麸质饮食对菌群组成的即时改变，例如在乳糜泻患者中，尽管GFD能恢复肠道菌群的α多样性，但其具体组成可能仍与健康人群存在差异 51。此外，其他研究也提示GFD可能导致长期菌群失衡，进而影响宿主免疫、营养吸收和代谢稳态 5253。缺乏长期队列研究，使得我们无法评估无麸质饮食是否会持续性地改变肠道微生态，以及这些改变是否会增加某些疾病的风险。
- 代谢综合征及相关指标： 代谢综合征（Metabolic Syndrome, MS）是一组代谢危险因素的集合，包括腹型肥胖、高血压、高血糖、血脂异常等，其发生发展是一个漫长的过程。虽然有研究指出，乳糜泻患者在严格无麸质饮食后，代谢综合征的发生率显著升高 54，但对于健康人群而言，无麸质饮食与代谢综合征风险之间的关系尚无定论 5556。现有研究多关注短期内的体重、血糖、血脂等指标，但这些指标的微小波动在短期内可能不具有临床意义，其真正的长期影响，例如是否会增加心血管疾病、2型糖尿病等慢性病的发生风险，需要至少数年甚至数十年的追踪才能得出可靠结论。
- 微量营养素缺乏的累积效应： 如前所述，无麸质饮食可能导致膳食纤维、B族维生素、铁、钙等微量营养素的摄入不足。短期内的营养素缺乏可能不会立即表现出明显的临床症状，但长期的边缘性缺乏可能对骨骼健康 5758、造血功能、神经功能等产生累积性负面影响。然而，现有研究往往未能提供足够长的随访时间来评估这些潜在的累积风险。
- 重金属积累： 一项横断面研究发现，无麸质饮食者尿液中总砷含量以及血液中汞、铅和镉的含量显著高于非无麸质饮食者，这可能与无麸质饮食中常见的鱼类和稻米等食物含有较高浓度的重金属有关 59。这项研究强调了长期无麸质饮食可能带来的重金属累积风险，但其长期健康后果，如是否会增加癌症、神经系统疾病等风险，仍需长期的纵向研究来证实。
- 食品添加剂的暴露： 无麸质加工食品为了改善口感和质地，往往会添加更多的食品添加剂。一项针对儿童的研究发现，患有乳糜泻的儿童比健康儿童接触某些食品添加剂（如黄原胶）的频率更高 60。然而，这些食品添加剂的长期累积暴露对人体健康的影响，特别是对肠道健康和代谢的影响，目前仍是一个研究空白。
综上所述，现有研究的时间维度局限性，使得我们无法全面评估无麸质饮食的长期益处或潜在风险。这种不确定性阻碍了制定基于充分科学证据的、针对非疾病人群的无麸质饮食指南。因此，亟需开展设计严谨、长期随访的队列研究，以填补这一知识空白。
5.2 跨学科研究的必要性探讨
鉴于当前无麸质饮食研究中存在的时间维度局限性以及其对健康人群潜在影响的不确定性，迫切需要开展更为全面和深入的跨学科研究。这将有助于弥合现有知识空白，为制定更精准、更具循证依据的饮食指南提供科学支撑。
跨学科合作的范畴与目标：
- 营养学与食品科学： 营养学家和食品科学家应紧密合作，深入研究无麸质替代食品的营养成分、加工工艺及其对人体营养摄入的影响。这包括开发营养更均衡、口感更好的无麸质产品，评估长期无麸质饮食对宏量和微量营养素吸收利用的真实影响，并探究如何通过膳食搭配或营养强化来弥补潜在的营养缺陷。例如，研究不同无麸质谷物和伪谷物（如藜麦、荞麦、苋菜籽）在营养组成上的优势，指导消费者进行更明智的选择。
- 胃肠病学与免疫学： 胃肠病学专家应继续深化对麸质相关疾病（如乳糜泻和非乳糜泻麸质敏感）病理生理机制的研究，明确不同个体对麸质反应的异质性，并探索新的生物标志物以实现更精准的诊断。免疫学家可以从分子层面解析麸质在不同人群中引发免疫反应的差异，为个性化饮食干预提供理论依据。例如，有研究指出，尽管乳糜泻患者通过无麸质饮食可以显著改善症状和肠道黏膜损伤，但仍有部分患者的肠道炎症指标（如CD3+和TCRγδ+细胞数量）未能完全恢复正常，这提示疾病的免疫学印记可能长期存在，需要进一步研究其临床意义 61。
- 微生物学与肠道生态学： 肠道菌群在消化、免疫和代谢中扮演着核心角色。微生物学家应与营养学家、胃肠病学家合作，通过宏基因组学、代谢组学等先进技术，系统研究长期无麸质饮食对健康人群肠道菌群结构、功能以及菌群-宿主互作的影响。重点关注无麸质饮食是否会导致有益菌群（如双歧杆菌、乳酸杆菌）的减少，以及这些改变是否与炎症、代谢紊乱等不良健康结局相关。例如，长期无麸质饮食可能导致肠道菌群多样性下降，并影响短链脂肪酸的产生，这需要深入探究其长期影响。
- 公共卫生学与流行病学： 公共卫生学者应承担起建立大型、长期队列研究的重任。这类研究需要招募大量健康个体，对其饮食习惯（包括是否遵循无麸质饮食）、健康状况、疾病发病率进行长期的追踪和监测。通过流行病学数据分析，可以揭示无麸质饮食与各种慢性疾病（如心血管疾病、糖尿病、某些癌症）之间的关联，评估其对整体人群健康的影响，并量化潜在的营养风险。这不仅需要多中心协作，还需要标准化的数据收集和分析方法。
- 心理学与社会学： 探讨无麸质饮食的社会心理影响同样重要。心理学家可以研究长期饮食限制对个体心理健康和生活质量的影响，特别是对社交活动和情绪状态的冲击。社会学家可以分析无麸质饮食潮流背后的社会文化因素，以及商业营销如何塑造公众认知，从而为更有效的健康教育和信息传播提供策略。
建立长期队列研究的必要性：
如前文所述，现有研究多为短期观察，难以捕捉无麸质饮食的长期累积效应。长期队列研究能够克服这一局限，提供关于：
- 营养状况的动态变化： 长期无麸质饮食是否导致特定营养素（如膳食纤维、B族维生素、铁、钙等）的慢性缺乏，以及这些缺乏是否在临床上表现出来。
- 疾病风险的长期演变： 评估无麸质饮食对代谢综合征、心血管疾病、自身免疫性疾病等慢性病发病风险的真实影响。
- 肠道微生态的稳定性和功能： 长期无麸质饮食对肠道菌群结构和功能的影响是否具有持久性，以及这些变化对宿主健康的具体贡献。
- 特殊人群的个体化需求： 细化不同遗传背景、生活习惯、健康状况个体对无麸质饮食的反应差异，从而实现更精准的个性化饮食建议。
通过多学科的深度融合与长期队列研究的开展，将有望全面解析无麸质饮食在健康与疾病中的复杂作用，为政府部门制定膳食指南、医疗机构提供临床建议、以及消费者做出明智的饮食选择提供坚实的科学依据，从而避免盲目跟风带来的潜在健康风险，并最大化其在医学治疗中的积极作用。
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参考文献
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Anastasia V Balakireva, Andrey A Zamyatnin
Nutrients. 2016 Oct 18;8(10):644. doi: 10.3390/nu8100644.
Theterm gluten intolerance may refer to three types of human disorders: autoimmune celiac disease (CD), allergy to wheat and non-celiac gluten sensitivity (NCGS). Gluten is a mixture of prolamin proteins present mostly in wheat, but also in barley, rye and oat. Gluten can be subdivided into three major groups: S-rich, S-poor and high molecular weight proteins. Prolamins within the groups possess similar structures and properties. All gluten proteins are evolutionarily connected and share the same ancestral origin. Gluten proteins are highly resistant to hydrolysis mediated by proteases of the human gastrointestinal tract. It results in emergence of pathogenic peptides, which cause CD and allergy in genetically predisposed people. There is a hierarchy of peptide toxicity and peptide recognition by T cells. Nowadays, there are several ways to detoxify gluten peptides: the most common is gluten-free diet (GFD), which has proved its effectiveness; prevention programs, enzymatic therapy, correction of gluten pathogenicity pathways and genetically modified grains with reduced immunotoxicity. A deep understanding of gluten intolerance underlying mechanisms and detailed knowledge of gluten properties may lead to the emergence of novel effective approaches for treatment of gluten-related disorders.
2Pathophysiology and immunogenetics of celiac disease.PubMed
Sara Aboulaghras, Daniela Piancatelli, Khadija Oumhani, et al.
Clin Chim Acta. 2022 Mar 1;528:74-83. doi: 10.1016/j.cca.2022.01.022. Epub 2022 Feb 1.
Celiac disease (CD) is a chronic inflammatory enteropathy caused by gluten (protein from wheat, rye and, barley) in genetically predisposed individuals carrying the HLA-DQ2/HLA-DQ8 genotype. This pathology has a multifactorial etiology in which HLA genes, the microbiome, gluten and, other environmental factors are involved in the development of the disease. Its pathogenesis involves both innate and adaptive immunity as well as upregulation of IL-15. The objective of this review is to examine the results of current studies on genetic and environmental variables to better understand the pathogenesis of this enteropathy. The complex etiology of celiac disease makes our understanding of the pathogenesis of the disease incomplete, and a better knowledge of the many genetic and environmental components would help us better understand the pathophysiology of celiac disease.
3Celiac disease.PubMed
Luis Rodrigo
World J Gastroenterol. 2006 Nov 7;12(41):6585-93. doi: 10.3748/wjg.v12.i41.6585.
Celiac disease (CD) is a common autoimmune disorder, induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief, this disorder is a protean systemic disease, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-II antigens, mainly of DQ2 and DQ8 classes. Previously, it was considered to be a rare childhood disorder, but is actually considered a frequent condition, present at any age, which may have multiple complications. Tissue transglutaminase-2 (tTG), appears to be an important component of this disease, both, in its pathogenesis and diagnosis. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive tTG auto-antibodies. The duodenal biopsy is considered to be the "gold standard" for diagnosis, but its practice has significant limitations in its interpretation, especially in adults. Occasionally, it results in a false-negative because of patchy mucosal changes and the presence of mucosal villous atrophy is often more severe in the proximal jejunum, usually not reached by endoscopic biopsies. CD is associated with increased rates of several diseases, such as iron deficiency anemia, osteoporosis, dermatitis herpetiformis, several neurologic and endocrine diseases, persistent chronic hypertransami-nasemia of unknown origin, various types of cancer and other autoimmune disorders. Treatment of CD dictates a strict, life-long gluten-free diet, which results in remission for most individuals, although its effect on some associated extraintestinal manifestations remains to be established.
4Celiac disease: a multi-faceted medical condition.PubMed
E M Domsa, I Berindan-Neagoe, I Para, et al.
J Physiol Pharmacol. 2020 Feb;71(1). doi: 10.26402/jpp.2020.1.01. Epub 2020 Apr 27.
Celiac disease (CD) is a systemic condition of autoimmune origin, affecting genetically predisposed individuals who at some point lose tolerance towards dietary gluten. Prevalence in the general population is 0.5 - 1%, with a higher frequency in women. The most important environmental factor for CD is ingestion of specific gluten peptides. It triggers a sequence of molecular events, involving the intestinal permeability and the immune system, which ends in damage of the intestinal mucosa. A number of studies have demonstrated the correlation between the intestinal microbiota and celiac disease. MicroRNAs through their regulatory role on gene expression have been implicated in the pathogenesis of CD and suggested as potential biomarkers. In the pediatric and adult population, CD displays different clusters of clinical symptoms. Persistent diarrhea, abdominal pain and involuntary weight loss are the classic symptoms of CD. In the majority of cases diagnosis relies on the combination of serum autoantibodies (anti-transglutaminase and anti-endomisium IgA) and duodenal biopsy showing villous atrophy, crypt hyperplasia and intraepithelial lymphocytes. Observance of a lifelong gluten-free diet, which interrupts the immune response to gluten peptides, is the only effective treatment of CD.
5Gluten Degrading Enzymes for Treatment of Celiac Disease.PubMed
Guoxian Wei, Eva J Helmerhorst, Ghassan Darwish, et al.
Nutrients. 2020 Jul 15;12(7):2095. doi: 10.3390/nu12072095.
Celiac disease (CeD) affects about 1% of most world populations. It presents a wide spectrum of clinical manifestations, ranging from minor symptoms to mild or severe malabsorption, and it may be associated with a wide variety of autoimmune diseases. CeD is triggered and maintained by the ingestion of gluten proteins from wheat and related grains. Gluten peptides that resist gastrointestinal digestion are antigenically presented to gluten specific T cells in the intestinal mucosa via HLA-DQ2 or HLA-DQ8, the necessary genetic predisposition for CeD. To date, there is no effective or approved treatment for CeD other than a strict adherence to a gluten-free diet, which is difficult to maintain in professional or social environments. Moreover, many patients with CeD have active disease despite diet adherence due to a high sensitivity to traces of gluten. Therefore, safe pharmacological treatments that complement the gluten-free diet are urgently needed. Oral enzyme therapy, employing gluten-degrading enzymes, is a promising therapeutic approach. A prerequisite is that such enzymes are active under gastro-duodenal conditions, quickly neutralize the T cell activating gluten peptides and are safe for human consumption. Several enzymes including prolyl endopeptidases, cysteine proteases and subtilisins can cleave the human digestion-resistant gluten peptides in vitro and in vivo. Examples are several prolyl endopeptidases from bacterial sources, subtilisins from that are natural oral colonizers and synthetic enzymes with optimized gluten-degrading activities. Without exception, these enzymes must cleave the otherwise unusual glutamine and proline-rich domains characteristic of antigenic gluten peptides. Moreover, they should be stable and active in both the acidic environment of the stomach and under near neutral pH in the duodenum. This review focuses on those enzymes that have been characterized and evaluated for the treatment of CeD, discussing their origin and activities, their clinical evaluation and challenges for therapeutic application. Novel developments include strategies like enteric coating and genetic modification to increase enzyme stability in the digestive tract.
6Non-celiac gluten sensitivity: Clinical presentation, etiology and differential diagnosis.PubMed
Marta Expósito Miranda, Luz García-Valdés, Elena Espigares-Rodríguez, et al.
Gastroenterol Hepatol. 2023 Aug-Sep;46(7):562-571. doi: 10.1016/j.gastrohep.2022.10.001. Epub 2022 Oct 13.
Non-celiac gluten sensitivity (NCGS) is the latest pathology incorporated into the group of gluten-related disorders. This review addresses the evidence on its etiology, differential diagnosis and symptomatology. Although NCGS is defined by a reaction to gluten, other possible etiopathogenic mechanisms have been described, such as an inadequate response to other components of wheat or to FODMAPs, with the term non-celiac sensitivity to wheat recently being extended. There are contradictory results on the validity of the diagnostic protocol of the Salerno experts. Evidence on diagnostic biomarkers for NCGS is scarce, although some studies indicate the following: antigliadin antibodies, zonulin, ALCAT test, micro-RNA, incRNA and certain cytokines. In NCGS, abdominal pain and fatigue are the most common symptoms. In addition, altered nutritional status is common. In conclusion, more research on NCGS is needed to improve understanding of its etiopathogenesis and clinical features.
7Non celiac gluten sensitivity and diagnostic challenges.PubMed
Giovanni Casella, Vincenzo Villanacci, Camillo Di Bella, et al.
Gastroenterol Hepatol Bed Bench. 2018 Summer;11(3):197-202.
Non-celiac gluten sensitivity (NCGS), also referred to as non-celiac wheat sensitivity (NCWS), is a clinical syndrome characterized by both intestinal and extra-intestinal symptoms responsive to the withdrawal of gluten-containing food from the diet. The aim of this review is to summarize recent advances in research and provide a brief overview of the history of the condition for the benefit of professionals working in gastroenterology. Academic databases such as PubMed and Google Scholar were searched using key words such as "non-celiac gluten sensitivity", "gluten related disorders", and the studies outlined in reference page were selected and analysed. Most of the analysed studiers agree that NCGS would need to be diagnosed only after exclusion of celiac disease and wheat allergy, and that a reliable serological marker is not available presently. The mechanisms causing symptoms in NCGS after gluten ingestion are largely unknown, but recent advances have begun to offer novel insights. The estimated prevalence of NCGS, at present, varies between 0.6 and 6%. There is an overlap between irritable bowel syndrome and NCGS with regard to the similarity of gastrointestinal symptoms. The histologic characteristics of NCGS are still under investigation, ranging from normal histology to slight increase in the number of T lymphocytes in the superficial epithelium of villi. Positive response to gluten free diet for a limited period (e.g., 6 weeks), followed by the reappearance of symptoms after gluten challenge appears, at this moment, to be the best approach for confirming diagnosis. The Salerno expert criteria may help to diagnose NCGS accurately in particular for research purposes but it has limited applicability in clinical practice.
8Nonceliac Gluten Sensitivity.PubMed
Maria Vazquez-Roque, Amy S Oxentenko
Mayo Clin Proc. 2015 Sep;90(9):1272-7. doi: 10.1016/j.mayocp.2015.07.009.
Nonceliac gluten sensitivity (NCGS) is the clinical term used to describe gastrointestinal (GI) and/or extraintestinal symptoms associated with gluten ingestion. The prevalence of NCGS is unknown. The condition has clinical features that overlap with those of celiac disease (CD) and wheat allergy (WA). The pathophysiologic process in NCGS is thought to be through an innate immune mechanism, whereas CD and WA are autoimmune- and allergen-mediated, respectively. However, dietary triggers other than gluten, such as the fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, have been implicated. Currently, no clinical biomarker is available to diagnose NCGS. Exclusion of CD and WA is necessary in the evaluation of a patient suspected to have NCGS. The onset of symptoms in patients with NCGS can occur within hours or days of gluten ingestion. Patients with NCGS have GI and extraintestinal symptoms that typically disappear when gluten-containing grains are eliminated from their diets. However, most patients suspected to have NCGS have already initiated a gluten-free diet at the time of an evaluation. A gluten elimination diet followed by a monitored open challenge of gluten intake to document recurrence of GI and/or extraintestinal symptoms can sometimes be helpful. If NCGS is strongly suggested, then a skilled dietitian with experience in counseling on gluten-free diets can provide proper patient education. Additional research studies are warranted to further our understanding of NCGS, including its pathogenesis and epidemiology, and to identify a biomarker to facilitate diagnosis and patient selection for proper management.
9Non-celiac gluten sensitivity: Time for sifting the grain.PubMed
Luca Elli, Leda Roncoroni, Maria Teresa Bardella
World J Gastroenterol. 2015 Jul 21;21(27):8221-6. doi: 10.3748/wjg.v21.i27.8221.
In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism (autoimmune in celiac disease and IgE-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity (NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.
10Nonceliac Gluten and Wheat Sensitivity.PubMed
Anam Khan, Milena Gould Suarez, Joseph A Murray
Clin Gastroenterol Hepatol. 2020 Aug;18(9):1913-1922.e1. doi: 10.1016/j.cgh.2019.04.009. Epub 2019 Apr 10.
Non-celiac gluten and/or wheat sensitivity (NCGS) is thought to be an immune-mediated reaction to gluten or other components of wheat (eg, fructans or amylase trypsin inhibitors) with intestinal and extraintestinal symptoms which improve once gluten and/or wheat is eliminated from the diet and after a diagnosis of celiac disease and wheat allergy have been excluded with appropriate testing. However, there is a great deal of skepticism within the scientific community questioning the existence of NCGS as a distinct clinical disorder. There are no strict diagnostic criteria and a placebo-controlled rechallenge trial has been recommended for diagnosis. In research settings, a double-blind placebo-controlled rechallenge trial has been recommended for diagnosis. There are limited studies estimating the prevalence of NCGS using this study design. The existing studies have variable results likely due to the lack of a uniform diagnostic criterion, a great deal of dependence on the patient's perception of symptoms and a large nocebo effect in existing studies. In clinical practice, a single blind placebo-controlled rechallenge trial has been recommended for diagnosis. The pathogenesis of NCGS is unclear and there is no known biomarker or diagnostic histologic lesion for this condition. It is important to adopt a multidisciplinary team approach to patients with suspected NCGS with involvement of the primary care doctor, gastroenterologist, pathologist and nutritionist who may play an important role in diagnosis and treatment. There may especially be a role in elimination of food containing high quantity of both gluten and fructans. Furthermore, patients should be educated on the nutritional implications of consuming a long-term gluten-free diet.
11Nonceliac gluten sensitivity: an approach to diagnosis and management.PubMed
Elizabeth M Collyer, Barbara S Kaplan
Curr Opin Pediatr. 2016 Oct;28(5):638-43. doi: 10.1097/MOP.0000000000000392.
PURPOSE OF REVIEW: Symptoms attributed to gluten consumption are frequently reported evoking the need for differentiating nonceliac gluten sensitivity (NCGS) from other gluten-related disorders such as celiac disease and wheat allergy. This review discusses diagnostic criteria and research to date on the pathogenesis and diagnosis of NCGS. RECENT FINDINGS: There is recent evidence to support NCGS as a distinct clinical entity. The symptoms attributed to NCGS are nonspecific, overlapping with those reported in patients with celiac disease and irritable bowel syndrome. In contrast to celiac disease and wheat allergy, the diagnosis of NCGS is more challenging because there are no specific clinical biomarkers and because the pathogenesis of NCGS is largely not well understood. The pathogenesis of NCGS may reflect alterations in innate immunity to gluten or other components of wheat, may be linked with autoimmunity, or is a result of a reaction to gluten as a fermentable carbohydrate. SUMMARY: NCGS is a newly characterized and evolving clinical entity that requires ruling out other causes of wheat-related or gluten-related gastrointestinal symptoms, including celiac disease and wheat allergy, coupled with double-blind placebo-controlled crossover challenge with gluten.
12Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity.PubMed
Luca Elli, Federica Branchi, Carolina Tomba, et al.
World J Gastroenterol. 2015 Jun 21;21(23):7110-9. doi: 10.3748/wjg.v21.i23.7110.
Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.
13Pitfalls in the Diagnosis of Coeliac Disease and Gluten-Related Disorders.PubMed
Annalisa Schiepatti, Jessica Savioli, Marta Vernero, et al.
Nutrients. 2020 Jun 7;12(6):1711. doi: 10.3390/nu12061711.
The spectrum of gluten-related disorders (GRD) has emerged as a relevant phenomenon possibly impacting on health care procedures and costs worldwide. Current classification of GRD is mainly based on their pathophysiology, and the following categories can be distinguished: immune-mediated disorders that include coeliac disease (CD), dermatitis herpetiformis (DH), and gluten ataxia (GA); allergic reactions such as wheat allergy (WA); and non-coeliac gluten sensitivity (NCGS), a condition characterized by both gastrointestinal and extra-intestinal symptoms subjectively believed to be induced by the ingestion of gluten/wheat that has recently gained popularity. Although CD, DH, and WA are well-defined clinical entities, whose diagnosis is based on specific diagnostic criteria, a diagnosis of NCGS may on the contrary be considered only after the exclusion of other organic disorders. Neither allergic nor autoimmune mechanisms have been found to be involved in NCGS. Mistakes in the diagnosis of GRD are still a relevant clinical problem that may result in overtreatment of patients being unnecessary started on a gluten-free diet and waste of health-care resources. On the basis of our clinical experience and literature, we aim to identify the main pitfalls in the diagnosis of CD and its complications, DH, and WA. We provide a practical methodological approach to guide clinicians on how to recognize and avoid them.
14Effects of Short-Term Gluten-Free Diet on Cardiovascular Biomarkers and Quality of Life in Healthy Individuals: A Prospective Interventional Study.PubMed
Simon Lange, Simeon Tsohataridis, Niklas Boland, et al.
Nutrients. 2024 Jul 13;16(14):2265. doi: 10.3390/nu16142265.
INTRODUCTION: The exposome concept includes nutrition as it significantly influences human health, impacting the onset and progression of diseases. Gluten-containing wheat products are an essential source of energy for the world's population. However, a rising number of non-celiac healthy individuals tend to reduce or completely avoid gluten-containing cereals for health reasons. AIM AND METHODS: This prospective interventional human study aimed to investigate whether short-term gluten avoidance improves cardiovascular endpoints and quality of life (QoL) in healthy volunteers. A cohort of 27 participants followed a strict gluten-free diet (GFD) for four weeks. Endothelial function measured by flow-mediated vasodilation (FMD), blood testing, plasma proteomics (Olink) and QoL as measured by the World Health Organisation Quality-of-Life (WHOQOL) survey were investigated. RESULTS: GFD resulted in decreased leucocyte count and C-reactive protein levels along with a trend of reduced inflammation biomarkers determined by plasma proteomics. A positive trend indicated improvement in FMD, whereas other cardiovascular endpoints remained unchanged. In addition, no improvement in QoL was observed. CONCLUSION: In healthy individuals, a short-term GFD demonstrated anti-inflammatory effects but did not result in overall cardiovascular improvement or enhanced quality of life.
15Effect of Gluten-Free Diet on Gut Microbiota Composition in Patients with Celiac Disease and Non-Celiac Gluten/Wheat Sensitivity.PubMed
Giacomo Caio, Lisa Lungaro, Nicola Segata, et al.
Nutrients. 2020 Jun 19;12(6):1832. doi: 10.3390/nu12061832.
Celiac disease (CD) and non-celiac gluten/wheat sensitivity (NCG/WS) are the two most frequent conditions belonging to gluten-related disorders (GRDs). Both these diseases are triggered and worsened by gluten proteins ingestion, although other components, such as amylase/trypsin inhibitors (ATI) and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), seem to be involved in the NCG/WS onset. Therefore, the only effective treatment to date is the long-life adherence to a strictly gluten-free diet. Recently, increasing attention has been paid to the intestinal barrier, a dynamic system comprising various components, which regulate the delicate crosstalk between metabolic, motor, neuroendocrine and immunological functions. Among the elements characterizing the intestinal barrier, the microbiota plays a key role, modulating the gut integrity maintenance, the immune response and the inflammation process, linked to the CD and NCG/WS outbreak. This narrative review addresses the most recent findings on the gut microbiota modulation induced by the gluten-free diet (GFD) in healthy, CD and NCG/WS patients.
16The Effect of Gluten-Free Diet on Health and the Gut Microbiota Cannot Be Extrapolated from One Population to Others.PubMed
Jose F Garcia-Mazcorro, Giuliana Noratto, Jose M Remes-Troche
Nutrients. 2018 Oct 4;10(10):1421. doi: 10.3390/nu10101421.
Gluten-related disorders (GRD) affect millions of people worldwide and have been related to the composition and metabolism of the gut microbiota. These disorders present differently in each patient and the only treatment available is a strict life-long gluten-free diet (GFD). Several studies have investigated the effect of a GFD on the gut microbiota of patients afflicted with GRD as well as healthy people. The purpose of this review is to persuade the biomedical community to think that, while useful, the results from the effect of GFD on health and the gut microbiota cannot be extrapolated from one population to others. This argument is primarily based on the highly individualized pattern of gut microbial composition and metabolic activity in each person, the variability of the gut microbiota over time and the plethora of factors associated with this variation. In addition, there is wide variation in the composition, economic viability, and possible deleterious effects to health among different GFD, both within and among countries. Overall, this paper encourages the conception of more collaborative efforts to study local populations in an effort to reach biologically and medically useful conclusions that truly contribute to improve health in patients afflicted with GRD.
17Gluten free diet and nutrient deficiencies: A review.PubMed
Giorgia Vici, Luca Belli, Massimiliano Biondi, et al.
Clin Nutr. 2016 Dec;35(6):1236-1241. doi: 10.1016/j.clnu.2016.05.002. Epub 2016 May 7.
BACKGROUND & AIMS: The only available treatment for celiac disease (CD) is lifelong adherence to gluten free (GF)-diet. However, GF-diet may lead to possible nutrient unbalance resulting in improper nutritional quality of diet. The aim of this study is to evaluate the nutritional quality of GF-diet. METHODS: MEDLINE/PubMed and Cochrane Library were electronically searched for articles published between 1990/01/01 and 2015/09/01. RESULTS: GF-diet was found to be poor in alimentary fiber due in particular to the necessary avoidance of several kinds of foods naturally rich in fiber (i.e. grain) and the low content of fiber of GF product that are usually made with starches and/or refined flours. Micronutrients are also found to be poor, in particular Vit. D, Vit. B12 and folate, in addition to some minerals such as iron, zinc, magnesium and calcium. Moreover, an inadequate macronutrient intake was reported related above all to the focus on the avoidance of gluten that often leaving back the importance of nutritional quality of the choice. In particular, it was found a higher content of both saturated and hydrogenated fatty acids and an increase in the glycemic index and glycemic load of the meal. CONCLUSIONS: Despite the GF-diet is necessary in celiac disease treatment and the attention is on gluten avoidance, the evaluation of nutritional quality of the diet must be considered. Moreover, educational strategies based on the relationship between nutrients and food and human health could be developed to optimize the therapeutic approach in celiac patients.
18A Review on the Gluten-Free Diet: Technological and Nutritional Challenges.PubMed
Dalia El Khoury, Skye Balfour-Ducharme, Iris J Joye
Nutrients. 2018 Oct 2;10(10):1410. doi: 10.3390/nu10101410.
Consumers, food manufacturers and health professionals are uniquely influenced by the growing popularity of the gluten-free diet. Consumer expectations have urged the food industry to continuously adjust and improve the formulations and processing techniques used in gluten-free product manufacturing. Health experts have been interested in the nutritional adequacy of the diet, as well as its effectiveness in managing gluten-related disorders and other conditions. In this review, we aim to provide a clear picture of the current motivations behind the use of gluten-free diets, as well as the technological and nutritional challenges of the diet as a whole. Alternative starches and flours, hydrocolloids, and fiber sources were found to play a complex role in mimicking the functional and sensory effects of gluten in gluten-free products. However, the quality of gluten-free alternatives is often still inferior to the gluten-containing products. Furthermore, the gluten-free diet has demonstrated benefits in managing some gluten-related disorders, though nutritional imbalances have been reported. As there is limited evidence supporting the use of the gluten-free diet beyond its role in managing gluten-related disorders, consumers are urged to be mindful of the sensorial limitations and nutritional inadequacies of the diet despite ongoing strategies to improve them.
19Gluten-free Diet, a Friend or a Foe, an American Perspective.PubMed
Tariq Alam, Gautam Saripalli, Sachin Rustgi
Plant Foods Hum Nutr. 2024 Dec 12;80(1):8. doi: 10.1007/s11130-024-01264-w.
Gluten proteins in cereal grains are often considered unsafe for health. Indeed, the dissemination of misinformation through various sources has led to a widespread misconception that the consumption of gluten by healthy individuals results in adverse health consequences and contributes to obesity. In recent years, many health-conscious consumers have started reducing or avoiding gluten consumption without a medical recommendation. Consequently, the adoption of gluten-free diets has expanded significantly. This study compared 39 gluten-free products and their gluten-containing counterparts for energy, sugar, dietary fiber content, and price. We found that, on average, gluten-free products available to United States consumers contained significantly less protein and more sugar and calories. Furthermore, on average, gluten-free products are more expensive than gluten-containing products. Our finding may serve as a guide for dietitians, nutritionists, and legislators in introducing a gluten-free prescription list for individuals with celiac disease, wheat allergy, and non-celiac wheat sensitivity.
20Associations between special diet and incidence risk of osteoporosis: a Mendelian randomization study.PubMed
Changwen Zhou, Lixue Yang, Ce Liu, et al.
Front Public Health. 2024 May 30;12:1364735. doi: 10.3389/fpubh.2024.1364735. eCollection 2024.
INTRODUCTION: Osteoporosis is a prevalent challenge in clinical orthopedics, affecting a significant percentage of individuals aged 50 and above. The goal of this study was to comprehensively understand the relationships between a specialized dietary regimen and the risk of developing osteoporosis. METHODS: This study employed extensive genome-wide association study (GWAS) summary statistics derived from the UK Biobank. It encompassed 8 kinds of special diets and 7 datasets pertaining to osteoporosis and associated symptoms. The principal analytical approach employed was the inverse-variance weighted method. Additionally, sensitivity analysis was employed to elucidate the diverse multiplicity patterns observed in the final model. RESULTS: Our results showed that there is significant evidence that a gluten-free diet is associated with osteoporosis [odds ratio (OR): 1.080, 95% confidence interval (CI): 1.048-1.112, = 4.23E-07)]. Furthermore, there exists a suggestive link between the three distinct dietary approaches and osteoporosis [(OR: 0.949, 95%CI: 0.929-0.970, = 3.00E-06) for comprehensive consumption; (OR: 1.053, 95%CI: 1.018-1.089, = 2.23E-03) for abstaining from wheat consumption; (OR: 1.036, 95%CI: 1.005-1.068, = 1.97E-02) for abstaining from sugar consumption]. No additional correlation between the special dietary regimens and osteoporosis has been observed. CONCLUSION: Our research has uncovered a notable correlation between a gluten-free diet and the occurrence of osteoporosis. Furthermore, it exerts a promoting influence on the onset of osteoporosis, which stands in direct contradiction to the therapeutic principles for Celiac Disease's complications. As such, a novel association among these three elements is postulated.
21Effects of Dietary Habits on Markers of Oxidative Stress in Subjects with Hashimoto's Thyroiditis: Comparison Between the Mediterranean Diet and a Gluten-Free Diet.PubMed
Martina Laganà, Tommaso Piticchio, Angela Alibrandi, et al.
Nutrients. 2025 Jan 20;17(2):363. doi: 10.3390/nu17020363.
BACKGROUND: The Mediterranean diet (MedD) exerts anti-inflammatory and anti-oxidant effects that are beneficial in autoimmune thyroid diseases (ATD). Recently, a gluten-free diet (GFD) has been proposed for non-celiac patients with Hashimoto's thyroiditis (HT), but its usefulness is under debate. The present pilot study evaluates the effects of these two dietary regimes, with a focus on redox homeostasis, in HT. PATIENTS AND METHODS: 45 euthyroid HT patients (30 F; median age 42 years) were randomly assigned to different dietary regimes: MedD ( = 15), GFD ( = 15) and free diet (FD, = 15). Thyroid function tests, autoantibodies, and oxidative stress markers (Advanced glycation end products, AGEs; glutathione peroxidase (GPx), thioredoxin reductase (TRxR), and total plasma antioxidant activity (TEAA) were measured at baseline and after 12 weeks. RESULTS: In the MedD group, significantly lower values of AGEs and higher values of GPX, TRX and TEAA with anti-oxidant action were detected ( < 0.05) at 12 weeks compared to baseline, and compared to the GFD and FD groups, in which the oxidative stress parameters did not change significantly ( > 0.05). No significant differences in serum levels of TSH, FT4, Ab-Tg, Ab-TPO compared to baseline were found in any group. CONCLUSIONS: This pilot study confirms the protective effect of the MedD against oxidative stress, while a GFD does not significantly influence markers of oxidative stress and/or thyroid autoimmunity/function parameters.
22Navigating the gluten-free boom.PubMed
Glenn A Gaesser, Siddhartha S Angadi
JAAPA. 2015 Aug;28(8). doi: 10.1097/01.JAA.0000469434.67572.a4.
Gluten-free diets have gained popularity with the public at a rate greater than would be expected based on the prevalence of gluten-related disorders such celiac disease, nonceliac gluten sensitivity, and wheat allergy. This article reviews gluten-related disorders, indications for gluten-free diets, and the possible health benefits of gluten. Despite the health claims for gluten-free eating, no published experimental evidence supports weight-loss with a gluten-free diet or suggests that the general population would benefit from avoiding gluten.
24Gluten-induced cognitive impairment ("brain fog") in coeliac disease.PubMed
Gregory W Yelland
J Gastroenterol Hepatol. 2017 Mar;32 Suppl 1:90-93. doi: 10.1111/jgh.13706.
Much is known about the serious neurological effects of gluten ingestion in coeliac disease patients, such as sporadic ataxia and peripheral neuropathy, although the causal links to gluten are still under debate. However, such disorders are observed in only a small percentage of coeliac patients. Much less is known about the transient cognitive impairments to memory, attention, executive function, and the speed of cognitive processing reported by the majority of patients with coeliac disease. These mild degradations of cognitive functions, referred to as "brain fog," are yet to be formally recognized as a medical or psychological condition. However, subtle tests of cognitive function are measurable in untreated patients with coeliac disease and improve over the first 12 months' therapy with a gluten-free diet. Such deficits also occur in patients with Crohn's disease, particularly in association with systemic inflammatory activity. Thus, cognitive impairments associated with brain fog are psychologically and neurologically real and improve with adherence to a gluten-free diet. There is not yet sufficient evidence to provide a definitive account of the mechanism by which gluten ingestion causes the impairments to cognitive function associated with brain fog, but current evidence suggests that it is more likely that the causal factor is not directly related to exposure to gluten.
25A systematic review and meta-analysis of the benefits of a gluten-free diet and/or casein-free diet for children with autism spectrum disorder.PubMed
Liuliu Quan, Xinjie Xu, Yonghong Cui, et al.
Nutr Rev. 2022 Apr 8;80(5):1237-1246. doi: 10.1093/nutrit/nuab073.
CONTEXT: It has been suggested that a gluten-free and casein-free (GFCF) diet may alleviate the symptoms of autism spectrum disorder (ASD) and facilitate neurodevelopment of children with ASD. Studies to date have been inconclusive. OBJECTIVE: This study aimed to evaluate (through quantitative meta-analysis) the efficacy and safety of a GFCF diet for children with ASD. To our knowledge, this is the first time such an analysis has been carried out. DATA SOURCES: Eight electronic databases were searched, from the establishment of each database up to March 27, 2020: PubMed, Web of Science, Embase (Ovid), PsycINFO (Ovid), Cochrane Library, CNKI, Wanfang, and VIP databases. DATA EXTRACTION: Two authors independently performed the data extraction and risk-of-bias assessment. DATA ANALYSIS: A quantitative meta-analysis was performed with standard procedures by using Stata SE 15 software. Within the total of 8 studies, with 297 participants, 5 studies reported significant reductions in stereotypical behaviors [standard mean difference (SMD) = -0.41, 95% confidence interval (CI): -0.68 to -0.15], and 3 studies reported improvements in cognition (SMD = -0.46, 95% CI: -0.91 to -0.01) following GFCF dietary intervention . No statistically significant changes were observed in other symptomatic categories (all P > 0.05). CONCLUSION: The current meta-analysis showed that a GFCF diet can reduce stereotypical behaviors and improve the cognition of children with ASD. Though most of the included studies were single-blind, the benefits of a GFCF diet that have been indicated are promising. Additional studies on a larger scale are warranted. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020177619.
26Efficacy and Safety of Diet Therapies in Children With Autism Spectrum Disorder: A Systematic Literature Review and Meta-Analysis.PubMed
Yuping Yu, Jinyue Huang, Xiaofang Chen, et al.
Front Neurol. 2022 Mar 14;13:844117. doi: 10.3389/fneur.2022.844117. eCollection 2022.
OBJECTIVE: Autism Spectrum Disorder is a neurodevelopmental disorder, with a rapid increase in recognition over the past decade. Interest in alternative therapies is growing annually, such as dietary therapies including gluten-free and/or casein-free diet, and the ketogenic diet. However, there is no consensus on the efficacy and safety of dietary therapy in children with ASD up to now. This study aimed to assess the efficacy and safety of these diet interventions for children with ASD based on a meta-analysis of global data. METHODS: Seven databases (Cochrane Library, PubMed, EMBASE, Web of Science, VIP, CNKI, and Wanfang) were searched according to the established inclusion criteria, from the inception of the databases to August 18, 2021. The Cochrane Bias risk assessment tool was intended to assess the quality of the included studies. Review Manager 5.4 software was used as an efficacy analysis tool of the included studies, taking the core autistic symptoms and scales of ASD as therapeutic efficacy evaluations. RESULTS: In total, 7 RCTs with 338 participants were finally obtained. All studies assessed the association between core autistic symptoms and therapeutic diet, showing a statistically significant effect (standard mean difference (SMD) of -0.51, 95% confidence interval (Cl): -0.81 to -0.21), in which two studies which followed the GFD diet reported significant reductions in social behaviors (SMD of-0.41, 95% Cl: -0.75 to -0.06), showing no correlation with the length of the interventions ( < 0.05). Two studies were performed in KD diet suggested a significant effect in core symptoms (SMD of -0.67, 95% Cl: -1.04 to -0.31). No statistically significant changes were observed in the GFCF diet, GFD diet, cognition, communication, and stereotypical behaviors subgroups (all > 0.05). CONCLUSION: The results of a meta-analysis suggest that diet therapies can significantly ameliorate core symptoms of ASD, and GFD diets are conducive to improving social behaviors. Although the results suggest the effectiveness of dietary therapy for ASD, limited by the small sample size of RCTs, more well-designed, and high-quality clinical trials are needed to validate the above conclusions. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021277565.
27Gluten-free and casein-free diets in the therapy of autism.PubMed
Klaus W Lange, Joachim Hauser, Andreas Reissmann
Curr Opin Clin Nutr Metab Care. 2015 Nov;18(6):572-5. doi: 10.1097/MCO.0000000000000228.
PURPOSE OF REVIEW: The purpose of this study is to discuss the role of gluten-free and casein-free diets in the treatment of autism. RECENT FINDINGS: In a recent UK survey, more than 80% of parents of children with autism spectrum disorder reported some kind of dietary intervention for their child (gluten-free and casein-free diet in 29%). When asked about the effects of the gluten-free and casein-free diet, 20-29% of the parents reported significant improvements on the autism spectrum disorder core dimensions. The findings of this study suggest additional effects of a gluten-free and casein-free diet on comorbid problems of autism such as gastrointestinal symptoms, concentration, and attention. The findings of another recent investigation suggested that age and certain urine compounds may predict the response of autism symptoms to a gluten-free and casein-free diet. Although these results need to be replicated, they highlight the importance of patient subgroup analysis. Intervention trials evaluating the effects of a gluten-free and casein-free diet on autistic symptoms have so far been contradictory and inconclusive. SUMMARY: Most investigations assessing the efficacy of a gluten-free and casein-free diet in the treatment of autism are seriously flawed. The evidence to support the therapeutic value of this diet is limited and weak. A gluten-free and casein-free diet should only be administered if an allergy or intolerance to nutritional gluten or casein is diagnosed.
28Gluten-free diet for pediatric patients with coeliac disease: A position paper from the ESPGHAN gastroenterology committee, special interest group in coeliac disease.PubMed
Veronica Luque, Paula Crespo-Escobar, Elin M Hård Af Segerstad, et al.
J Pediatr Gastroenterol Nutr. 2024 Apr;78(4):973-995. doi: 10.1002/jpn3.12079. Epub 2024 Jan 30.
BACKGROUND AND OBJECTIVE: Coeliac disease is a chronic, immune-mediated disorder for which the only treatment consists of lifelong strict adherence to gluten-free diet (GFD). However, there is a lack of evidence-based guidelines on the GFD dietary management of coeliac disease. This position paper, led by the Special Interest Group in coeliac disease of the European Society of Pediatric, Gastroenterology Hepatology, and Nutrition, supported by the Nutrition Committee and the Allied Health Professionals Committee, aims to present evidence-based recommendations on the GFD as well as how to support dietary adherence. METHODS: A wide literature search was performed using the MeSH Terms: "diet, gluten free," "gluten-free diet," "diets, gluten-free," "gluten free diet," and "coeliac disease" in Pubmed until November 8th, 2022. RESULTS: The manuscript provides an overview of the definition of the GFD, regulations as basis to define the term "gluten-free," which foods are naturally gluten-free and gluten-containing. Moreover, it provides recommendations and educational tips and infographics on suitable food substitutes, the importance of reading food labels, risk of gluten cross-contact at home and in public settings, nutritional considerations as well as factors associated to dietary adherence based on available evidence, or otherwise clinical expertise. CONCLUSIONS: This position paper provides guidance and recommendations to support children with coeliac disease to safely adhere to a GFD.
29Diet and Psoriasis-Related Information on Instagram: A Quality and Content Analysis of Posts Under Popular Psoriasis Hashtags.PubMed
Sabrina Cowan, Poppy Hawkins, Ghislaine Marks, et al.
J Hum Nutr Diet. 2025 Apr;38(2):e70034. doi: 10.1111/jhn.70034.
BACKGROUND: Psoriasis is a chronic immune-mediated skin condition. Evidence supporting dietary management of psoriasis is limited. However, People Living with Psoriasis (PLwP) trial dietary interventions as a management strategy, often taken from popular literature. Social media is a popular source of nutrition information. However, little is known about the dietary information suggested for psoriasis on these platforms. The aim of this study was to explore the dietary approaches suggested for psoriasis on Instagram and evaluate their quality. METHODOLOGY: Cross-sectional content analysis of Instagram posts providing dietary information for plaque psoriasis management, posted under the 12 most popular psoriasis hashtags. Posts were evaluated for quality using the DISCERN instrument. RESULTS: Overall, 138 Instagram posts were analysed. The most common type of dietary recommendation was 'exclusion', most frequently of alcohol and dairy. Detox and 'clean eating' were also frequently mentioned, as well as the inclusion of protein, and adherence to a gluten-free diet. The most common content creators were those with those with lived experience of psoriasis (29.7%). None of the posts were created by qualified nutrition professionals and only 6.5% were by healthcare professionals (HCPs). The majority (99%) of posts identified were of 'poor' quality. CONCLUSION: Most dietary information on Instagram for managing psoriasis is poor quality, restrictive, unsubstantiated and shared by non-HCPs. Therefore, PLwP may be subject to dietary misinformation when using Instagram. HCPs should be equipped to counter diet and psoriasis misinformation. Further research is needed to investigate appropriate ways to provide dietary support for PLwP.
30Gluten and FODMAPS-Sense of a Restriction/When Is Restriction Necessary?PubMed
Walburga Dieterich, Yurdagül Zopf
Nutrients. 2019 Aug 20;11(8):1957. doi: 10.3390/nu11081957.
Gluten-free diet (GFD) is enjoying increasingly popularity, although gluten-free products are considerably more expensive. GFD is absolutely necessary for patients with celiac disease, as in this case even minor amounts of gluten can lead to the destruction of the intestinal mucosa. In addition, GFD is currently the best therapy to improve clinical symptoms of patients with non-celiac gluten sensitivity (NCGS), although the diet may not be as strict as that for patients with celiac disease. Beside gluten, other wheat components such as oligosaccharides and amylase trypsin inhibitors are discussed as triggers of NCGS in this review. An overlap between gastrointestinal symptoms in NCGS and irritable bowel syndrome (IBS) is described. Patients with NCGS attribute their symptoms to the consumption of gluten, while patients with IBS rarely describe gluten as a trigger. Recently, several studies have demonstrated that the introduction of a low FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) diet reduced gastrointestinal symptoms in patients with IBS and this diet is suggested as the first choice of therapy in IBS. However, a low FODMAP diet also eliminates prebiotica and may negatively influence the gut microbiota. For this reason, the diet should be liberalized after symptom improvement. There is no evidence that a GFD is healthier than the standard diet. In contrast, GFD often is accompanied by nutritional deficiencies, mainly minerals and vitamins. Therefore, GFD and low FODMAP diets are not recommended for healthy subjects. Since wheat contains fructans belonging to FODMAPs), a GFD is not only gluten-free but also has less FODMAPs. Thus, symptom improvement cannot be correctly correlated with the reduction of either one or the other.
31Review article: Systemic consequences of coeliac disease.PubMed
Pilvi Laurikka, Laura Kivelä, Kalle Kurppa, et al.
Aliment Pharmacol Ther. 2022 Jul;56 Suppl 1(Suppl 1):S64-S72. doi: 10.1111/apt.16912.
BACKGROUND: The best-known symptoms of coeliac disease are related to the gastrointestinal tract, but the disease may also present with various systemic manifestations outside the intestine. Some of these consequences may remain permanent in undiagnosed individuals or if the diagnostic delay is prolonged. However, for many of the systemic manifestations, the scientific evidence remains scant and contradictory. AIMS AND METHODS: We conducted a narrative review of the most thoroughly studied and clinically relevant systemic consequences of coeliac disease, especially those that could be prevented or alleviated by early diagnosis. The review is intended particularly for physicians encountering these patients in daily clinical practice. RESULTS: The possible systemic consequences of coeliac disease extend to multiple organ systems, the best studied of which are related to skeletal, reproductive, cardiovascular and neurological systems. Furthermore, the disease is associated with an elevated risk of psychiatric comorbidities, non-Hodgkin lymphomas and intestinal adenocarcinoma. CONCLUSIONS: The various systemic consequences of coeliac disease play a significant role in the overall health of patients. Early diagnosis and treatment with a gluten-free diet appear to be beneficial for most, but not all of these conditions. The possible negative metabolic and psychosocial effects of the diet should be acknowledged during follow-up.
32Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review.PubMed
Eirini Bathrellou, Meropi D Kontogianni, Demosthenes B Panagiotakos
Maturitas. 2018 Jun;112:29-33. doi: 10.1016/j.maturitas.2018.03.014. Epub 2018 Mar 30.
Celiac disease (CD) and non-gluten (or wheat) sensitivity (NCGS) are two gluten-related disorders, the treatment of which relies on dietary withdrawal of gluten (absolute and lifelong in the case of CD patients). However, these conditions differ in their pathophysiology and impact on health. CD is an autoimmune disorder of the intestine, and is associated with a wide range of disorders, pre- and post-diagnosis. Its autoimmune and inflammatory nature raises concerns about its potential effects on mortality and morbidity. Here we review the data on the health impact CD or NCGS may have prospectively, and report on the role of a gluten-free diet (GFD) in this respect. Since study designs have been heterogeneous, we focus on studies of treated patients with a biopsy-proven diagnosis of CD, to eliminate possible bias from misdiagnosis. The review revealed a moderately increased mortality risk among CD patients, mainly attributed to cardiovascular disease and malignancy. Other long-term morbidities of CD include autoimmune disorders, nutritional deficiencies, impaired bone health, reproductive abnormalities, and neurologic and neuropsychiatric disorders, which are substantially improved, and some of them even completely treated, after strict adherence to a GFD. For NCGS, the literature is too limited and its long-term complications are unknown.
33A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects.PubMed
M Barone, N Della Valle, R Rosania, et al.
Eur J Clin Nutr. 2016 Jan;70(1):23-7. doi: 10.1038/ejcn.2015.114. Epub 2015 Jul 15.
BACKGROUND/OBJECTIVES: There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers. SUBJECTS/METHODS: Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients' BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary. RESULTS: At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively). CONCLUSIONS: Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.
34Celiac disease and the gluten-free diet: consequences and recommendations for improvement.PubMed
Thimmaiah G Theethira, Melinda Dennis
Dig Dis. 2015;33(2):175-182. doi: 10.1159/000369504. Epub 2015 Apr 22.
BACKGROUND: Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically susceptible individuals. CD-related enteropathy leads to multiple nutritional deficiencies involving macro- and micronutrients. Currently, medical nutrition therapy consisting of the gluten-free diet (GFD) is the only accepted treatment for CD. KEY MESSAGES: The GFD is the cornerstone of treatment for CD. Prior published studies have concluded that maintenance of the GFD results in improvement of the majority of nutritional deficiencies. In the past, counseling for CD focused mainly on the elimination of gluten in the diet. However, the GFD is not without its inadequacies; compliance to the GFD may result in certain deficiencies such as fiber, B vitamins, iron, and trace minerals. Paucity of fortified gluten-free foods may be responsible for certain deficiencies which develop on the GFD. Weight gain and obesity have been added to the list of nutritional consequences while on the GFD and have been partially attributed to hypercaloric content of commercially available gluten-free foods. Follow-up of patients diagnosed with CD after starting the GFD has been reported to be irregular and, hence, less than ideal. CONCLUSIONS: Monitoring of the nutritional status using blood tests and use of appropriate gluten-free supplementation are integral components in the management of CD. The ideal GFD should be nutrient-dense with naturally gluten-free foods, balanced with macro- and micronutrients, reasonably priced, and easily accessible. Rotation of the pseudo-cereals provides a good source of complex carbohydrates, protein, fiber, fatty acids, vitamins and minerals. Fortification/enrichment of commonly consumed gluten-free commercial grain products should be encouraged. Dietitians specializing in CD play a critical role in the education and maintenance of the GFD for patients with CD.
35Gluten-Free Diet Indications, Safety, Quality, Labels, and Challenges.PubMed
Kamran Rostami, Justine Bold, Alison Parr, et al.
Nutrients. 2017 Aug 8;9(8):846. doi: 10.3390/nu9080846.
A gluten-free diet (GFD) is the safest treatment modality in patient with coeliac disease (CD) and other gluten-related disorders. Contamination and diet compliance are important factors behind persistent symptoms in patients with gluten related-disorders, in particular CD. How much gluten can be tolerated, how safe are the current gluten-free (GF) products, what are the benefits and side effects of GFD? Recent studies published in on gluten-free products' quality, availability, safety, as well as challenges related to a GFD are discussed.
36Gluten-Free Diet in Prisons in Poland: Nutrient Contents and Implementation of Dietary Reference Intake Standards.PubMed
Aureliusz Kosendiak, Piotr Stanikowski, Dorota Domagała, et al.
Nutrients. 2020 Sep 16;12(9):2829. doi: 10.3390/nu12092829.
The gluten-free diet (GFD) requires special attention from nutritionists due to the potential risk of nutrient deficiencies in its users. This risk may be greater when this type of nutrition is implemented in prisons due to the limited possibilities of external control, a low catering budget for meals, and insufficiently defined recommendations regulating nutrition for prisoners. The aim of the present study was to assess the nutritional value of GFD and regular diet meals served in some Polish prisons and to compare the values to the dietary reference intake (DRI) standards. Using a specialized computer program, 7-day menus of both types of diet provided in 10 prisons were analyzed. The percentage coverage of the DRI was calculated based on the recommendations of the Polish National Food and Nutrition Institute. GFD was characterized by lower average contents of energy and 11 out of 14 essential nutrients, i.e., protein, carbohydrates, dietary fiber, starch, ash, sodium, calcium, iron, zinc, folate, and vitamin B. The average content of phosphorus, niacin, and riboflavin in the gluten-free diet was higher than that in the regular diet. It was shown that the meals in GFD and the regular diet did not provide the recommended amounts of calcium (38 and 44% DRI, respectively), vitamin D (29 and 30% DRI), vitamin C (86 and 76% DRI), and folate (51 and 56% DRI). In turn, the supply of sodium, phosphorus, copper, and vitamins A and B substantially exceeded the recommended levels. The results indicate a need for greater quality control of GFD meals served in catering facilities. It is also necessary to develop legal provisions that will regulate more specifically the nutrition for prisoners in terms of an adequate supply of minerals and vitamins.
37The Handbook of Minerals on a Gluten-Free Diet.PubMed
Iga Rybicka
Nutrients. 2018 Nov 5;10(11):1683. doi: 10.3390/nu10111683.
The importance of a gluten-free diet (GFD) in the treatment of celiac disease and other gluten-related disorders is undisputable. However, strict GFD often lead to nutritional imbalances and, therefore, to deficiencies. One of the most common deficiencies from a GFD are an insufficient amount of Ca, Fe, Mg, and Zn. This is mainly because the most of popular gluten-free (GF) raw materials are poor in minerals. Although the popularity of GFD is constantly growing, the data on minerals in GF products are still limited. More importantly, an access to the data is even more restricted. Therefore, the paper reviews the Ca, Fe, Mg, and Zn contents in hundreds of grain GF products available worldwide. The data for 444 products from categories of flours, mixes for cooking, bakery products, cereals, groats, rice, and pasta are obtained from research papers and nutritional databases. The calculation of the realization of mineral requirements from a portion of each product with its graphical classification as rich/average/poor source of each mineral is given. The review is a handbook of minerals for people on a GFD, dietitians, and food producers.
38Nutritional Considerations in Celiac Disease and Non-Celiac Gluten/Wheat Sensitivity.PubMed
Fardowsa Abdi, Saania Zuberi, Jedid-Jah Blom, et al.
Nutrients. 2023 Mar 19;15(6):1475. doi: 10.3390/nu15061475.
A gluten-free diet (GFD) is the only available treatment for celiac disease (CeD), and it may also improve symptoms in non-celiac gluten/wheat sensitivity (NCGWS). In CeD, gluten triggers an immune reaction leading to enteropathy, malabsorption, and symptoms; in NCGWS, the mechanism leading to symptoms is unknown, and neither wheat nor gluten triggers enteropathy or malabsorption. A strict GFD is, therefore, necessary for CeD, but a gluten-restricted diet (GRD) may suffice to achieve symptom control for NCGWS. Regardless of this distinction, the risk of malnutrition and macro- and micronutrient deficiencies is increased by the adoption of a GFD or GRD. Thus, patients with CeD or NCGWS should undergo nutritional assessment and subsequent monitoring, based on evidence-based tools, under the care of a multidisciplinary team involving physicians and dietitians, for the long-term management of their nutrition. This review gives an overview of available nutrition assessment tools and considerations for the nutritional management of CeD and NCGWS populations.
39Nutritional Status in Spanish Children and Adolescents with Celiac Disease on a Gluten Free Diet Compared to Non-Celiac Disease Controls.PubMed
Catalina Ballestero Fernández, Gregorio Varela-Moreiras, Natalia Úbeda, et al.
Nutrients. 2019 Oct 1;11(10):2329. doi: 10.3390/nu11102329.
Patients who follow a gluten-free diet (GFD) may be prone to nutritional deficiencies, due to food restriction and consumption of gluten-free products. The aim was to assess nutritional status in celiac children and adolescents on a long-term GFD. A cross-sectional age and gender-matched study in 70 celiac and 67 non-celiac volunteers was conducted, using dietary, anthropometric, biochemical parameters, and assessing bone mineral density and physical activity. Adequacy of vitamin D intake to recommendations was very low, in both groups, and intakes for calcium and magnesium were significantly lower in celiac volunteers. Celiac children and adolescents may have a higher risk of iron and folate deficiencies. Both groups followed a high-lipid, high-protein, low fiber diet. Median vitamin D plasma levels fell below reference values, in celiac and non-celiac participants, and were significantly lower in celiac girls. Other biochemical parameters were within normal ranges. Anthropometry and bone mineral density were similar within groups. With the exception of some slightly lower intakes, children and adolescents following a GFD appear to follow the same trends as healthy individuals on a normal diet. No effect of food restriction or gluten-free product consumption was observed.
40Gluten-Free Diet and Other Celiac Disease Therapies: Current Understanding and Emerging Strategies.PubMed
Anna Maria Mazzola, Irene Zammarchi, Maria Chiara Valerii, et al.
Nutrients. 2024 Mar 29;16(7):1006. doi: 10.3390/nu16071006.
A lifelong gluten-free diet (GFD) is the only treatment for celiac disease and other gluten-related disorders. Nevertheless, strict adherence to the GFD is often challenging due to concerns about social isolation, risk of gluten contaminations, high cost, poor quality and the taste of gluten-free products. Moreover, although the GFD is effective in achieving mucosal healing, it may lead to dietary imbalances due to nutrient deficiencies over a long period of time. To overcome these issues, several gluten-free wheat flours have been developed to create products that closely resemble their gluten-containing counterparts. Furthermore, given the critical importance of adhering to the GFD, it becomes essential to promote adherence and monitor possible voluntary or involuntary transgressions. Various methods, including clinical assessment, questionnaires, serology for celiac disease, duodenal biopsies and the detection of Gluten Immunogenic Peptides (GIPs) are employed for this purpose, but none are considered entirely satisfactory. Since adherence to the GFD poses challenges, alternative therapies should be implemented in the coming years to improve treatment efficacy and the quality of life of patients with celiac disease. The aim of this narrative review is to explore current knowledge of the GFD and investigate its future perspectives, focusing on technology advancements, follow-up strategies and insights into a rapidly changing future.
41The Gluten-Free Diet for Celiac Disease and Beyond.PubMed
Bara Aljada, Ahmed Zohni, Wael El-Matary
Nutrients. 2021 Nov 9;13(11):3993. doi: 10.3390/nu13113993.
The gluten-free diet (GFD) has gained popularity beyond its main medical indication as the treatment for gluten-induced immune-mediated disorders such as celiac disease (CD), dermatitis herpetiformis, gluten ataxia, wheat allergy, and non-celiac gluten sensitivity. However, the diet carries some disadvantages such as elevated costs, nutritional deficiencies, and social and psychological barriers. The present work aims to review indications, proven benefits, and adverse events of a gluten-free diet. Close follow-up with patients following the diet is recommended. More data is needed to assess the effectiveness of the diet in managing mental and cognitive disorders and to establish a connection between the brain and gluten.
42Gluten-Free Diet for Fashion or Necessity? Review with New Speculations on Irritable Bowel Syndrome-like Disorders.PubMed
Raffaele Borghini, Alessia Spagnuolo, Giuseppe Donato, et al.
Nutrients. 2024 Dec 8;16(23):4236. doi: 10.3390/nu16234236.
Nowadays, the gluten-free diet (GFD) has become much more than the dietary treatment for celiac disease. Due to its presumed beneficial effects even in non-celiac subjects, it has become a new fashion statement and it is promoted by some healthcare professionals, social media and marketing strategists. On the other hand, regardless of a proper medical indication, a GFD may present side effects, such as poor palatability, high costs and socio-psychological adversities. Moreover, it can be an obstacle to correct clinical practice and may induce nutritional deficiency due to a low-quality diet. In addition, a GFD can trigger or exacerbate many irritable bowel syndrome (IBS)-like disorders in predisposed subjects: reactivity to dietary nickel, the increased consumption of FODMAP-rich foods and histamine intolerance seem to frequently play a relevant role. The possible intersections between high-risk foods in these categories of patients, as well as the possible overlaps among IBS-like disorders during GFD, are described. In conclusion, it is advisable to undergo a careful clinical evaluation by a gastroenterologist and a nutritionist (in some cases, also a psychotherapist) before starting and during a GFD, because both benefits and risks are possible. It is also important to take into account IBS-like disorders that can be exacerbated by a GFD and that are still underestimated today.
43Persistent Iron Deficiency Anemia in Patients with Celiac Disease Despite a Gluten-Free Diet.PubMed
Gianpiero Stefanelli, Angelo Viscido, Salvatore Longo, et al.
Nutrients. 2020 Jul 22;12(8):2176. doi: 10.3390/nu12082176.
Celiac disease (CD) is an autoimmune disorder characterized by intolerance to dietary gluten in genetically predisposed subjects. Iron deficiency anemia (IDA) is a common sign in CD, being the only abnormality in approximately 40% of celiac patients. A multifactorial etiology leads to IDA in CD. The two main causes are the villous atrophy of the mucosa at the site of iron absorption (the duodenum) and the resulting inflammation, which triggers the mechanism that leads to the anemia of chronic disease. Until now, it has been unclear why some patients with CD continue to have IDA despite a careful gluten-free diet (GFD) and the normalization of villous atrophy. Furthermore, some celiac patients are refractory to oral iron supplementation despite the healing of the mucosa, and they thus require periodic intravenous iron administration. The Marsh classification evaluates the degree of inflammation and villous atrophy, but it does not assess the possible persistence of ultrastructural and molecular alterations in enterocytes. The latter was found in CD in remission after adopting a GFD and could be responsible for the persistently reduced absorption of iron and IDA. Even in non-celiac gluten sensitivity, anemia is present in 18.5-22% of patients and appears to be related to ultrastructural and molecular alterations in intestinal microvilli. It is possible that a genetic component may also play a role in IDA. In this review, we evaluate and discuss the main mechanisms of IDA in CD and the possible causes of its persistence after adopting a GFD, as well as their therapeutic implications.
44Current applications of gluten-free grains - a review.PubMed
Joseph S Woomer, Akinbode A Adedeji
Crit Rev Food Sci Nutr. 2021;61(1):14-24. doi: 10.1080/10408398.2020.1713724. Epub 2020 Jan 22.
The population of Americans suffering from celiac, gluten intolerance, and wheat allergy is 1 in every 14 people. Also, many are choosing gluten-free (GF) diets nowadays because of the perception that it is a healthier option for them. Therefore, in the last decade, the GF market in the US and all over the world has seen significant growth. Globally, GF product sales reached 4.63 billion USD in 2017, and are expected to reach 6.47 billion USD by 2023, a projected compound annual growth rate of 7.6%. Several grains like millet, corn, sorghum, and pseudocereals like amaranth, quinoa, and teff are the main ingredients for a gluten diet. Though most of them have a comparable nutrient profile as common grains, the main challenge to their acceptability is the quality departure from gluten-containing counterparts and imbalance nutrients that ensue when food processing aids like starch, gums, and enzymes are used. In this review, we profiled some of the common grains, their characteristics, functionality and the various food types they are used for. We also reviewed the impact of some of the current food processing aids like starch, hydrocolloids used for improving functionality, and processing techniques like extrusion suitable for making remarkable GF foods.
45Effects of a gluten-free diet on gut microbiota and immune function in healthy adult humans.PubMed
Yolanda Sanz
Gut Microbes. 2010 May-Jun;1(3):135-7. doi: 10.4161/gmic.1.3.11868. Epub 2010 Mar 16.
Diet is a major environmental factor influencing gut microbiota diversity and functionality, which might be relevant to subjects following dietary therapies. Celiac disease (CD) is an enteropathy caused by an aberrant immune response to cereal gluten proteins and the only therapy is the adherence to a gluten-free diet (GFD). In this context, a preliminary study was conducted to establish whether the GFD in itself could modify the composition and immune properties of the gut microbiota. The trial included 10 healthy subjects (30.3 years-old), which were submitted to a GFD over one month. Analysis of fecal microbiota and dietary intake indicated that numbers of healthy gut bacteria decreased, while numbers of unhealthy bacteria increased parallel to reductions in the intake of polysaccharides after following the GFD. Fecal samples of subjects under a GFD, which represent an altered microbiota, also exerted lower immune stimulatory effects on peripheral blood mononuclear cells than those of subjects on a regular gluten-containing diet. This addendum presents further discussion on the rationale behind these findings, limitations of the study and possible consequences of dietary counselling in the care process of celiac disease patients.
46Nutritional and Nutraceutical Properties of Selected Pulses to Promote Gluten-Free Food Products.PubMed
M Jaqueline Palomares-Navarro, Vanessa Sánchez-Quezada, Julián J Palomares-Navarro, et al.
Plant Foods Hum Nutr. 2023 Jun;78(2):253-260. doi: 10.1007/s11130-023-01060-y. Epub 2023 Jun 8.
The market for gluten-free products is increasing with an estimated 7.6% annual growth rate from 2020 to 2027. It has been reported that most gluten-free products, such as bread, cookies, and pasta, contain great amounts of simple carbohydrates and are low in fiber and protein, affecting people's health. Pulses such as common beans, chickpeas, lentils, and peas have been studied as an alternative for developing gluten-free products because of their high protein and fiber content. In addition, they contain bioactive compounds with nutraceutical properties, such as phenolics, saponins, dietary fiber, and resistant starch, among others. Most studies carried out with pulses in vitro and in vivo have displayed health benefits, proving that pulse-based food products are better than their counterparts, even those containing wheat, with proper sensory acceptance. This work reviews pulse's nutritional and nutraceutical properties to promote the development and consumption of gluten-free products and improve their formulations to promote people's health.
47Gluten content in labeled and unlabeled gluten-free food products used by patients with celiac disease.PubMed
Wajiha Mehtab, Vikas Sachdev, Alka Singh, et al.
Eur J Clin Nutr. 2021 Aug;75(8):1245-1253. doi: 10.1038/s41430-020-00854-6. Epub 2021 Jan 18.
OBJECTIVE: Gluten-free (GF) diet is the only reliable treatment for patients with celiac disease (CeD), but data on the extent of gluten contamination in GF food available in India is scanty. We evaluated gluten content in labeled, imported, and non-labeled GF food products currently available in the Indian market. METHODS: Overall, 794 processed and commercially available packaged GF products (labeled GF (n = 360), imported GF (n = 80), and non-labeled/naturally GF (n = 354)) were collected from supermarkets of National Capital Region of India. Those unavailable in stores were purchased from e-commerce sites or directly from the manufacturers. Gluten level in them was determined by Ridascreen Gliadin sandwich R5 enzyme-linked immunosorbent assay (R-Biopharm AG, Germany). As per Codex Alimentarius and Food Safety and Standard Authority of India, "gluten free" labeled products must not contain > 20 mg/kg of gluten. RESULTS: Overall, 10.1% of 794 GF products including 38 (10.8%) of 360 labeled and 42 (11.8%) of 354 non-labeled/naturally GF food products had gluten content > 20 mg/kg (range: 24.43-355 and 23.2-463.8 mg/kg, respectively). None of the imported GF products had gluten more than the recommended limits. Contaminated products most commonly belonged to cereal and their products (flours, coarse grains, pasta/macaroni, snack foods) pulse flours, spices, and bakery items. CONCLUSIONS: A substantial proportion (10.1%) of GF food products (both labeled and non-labeled) available in India have gluten content greater than the prescribed limits of <20 mg/kg. Physicians, dietitians, support group, and patients with CeD should be made aware of this fact and regulatory bodies should ensure quality assurance.
48Gluten contamination in the Canadian commercial oat supply.PubMed
T B Koerner, C Cléroux, C Poirier, et al.
Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2011 Jun;28(6):705-10. doi: 10.1080/19440049.2011.579626.
A growing body of evidence suggests that a majority of people with celiac disease and on a gluten-free diet can safely consume pure oats in moderate amounts; however, previous studies have indicated that the commercial oat supply in other countries, and in Canada to some extent, is contaminated with other grains. This study has confirmed that the commercial oat supply in Canada is heavily contaminated with gluten from other grains. Approximately 88% of the oat samples (n = 133) were contaminated above 20 mg kg(-1) and there were no differences between the oat types tested. Only one gluten-free variety of oats was analysed and it consistently provided negative results in all analyses. It is difficult to determine where the contamination originates, but there are possibilities for cross-contamination in the field, in the transport of the grain, in the storage of the grain, and in the milling and packaging facilities. It is clear from this study that only those products that have been certified 'pure' oats would be appropriate for a gluten-free diet.
49Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue.PubMed
M Cristina P de Souza, Marie-Eve Deschênes, Suzanne Laurencelle, et al.
Can J Gastroenterol Hepatol. 2016;2016:1576360. doi: 10.1155/2016/1576360. Epub 2016 Apr 14.
The question about recommending pure, noncontaminated oats as part of the gluten-free diet of patients with celiac disease remains controversial. This might be due to gluten cross contamination and to the possible immunogenicity of some oat cultivars. In view of this controversy, a review of the scientific literature was conducted to highlight the latest findings published between 2008 and 2014 to examine the current knowledge on oats safety and celiac disease in Europe and North America. Results showed that regular oats consumed in Canada are largely contaminated. Overall, the consumption of pure oats has been generally considered to be safe for adults and children. However, it appears that some oat cultivars may trigger an immune response in sensitive individuals. Therefore, further long-term studies on the impact of consumption of oats identifying the cultivar(s) constitute an important step forward for drawing final recommendations. Furthermore, a closer and more accurate monitoring of the dietary intake of noncontaminated oats would be paramount to better determine what its actual contribution in the gluten-free diet of adults and children with celiac disease are in order to draw sound recommendations on the safety of pure oats as part of the gluten-free diet.
50Assessment of Avenins from Different Oat Varieties Using R5-Based Sandwich ELISA.PubMed
Lora Benoit, Jongkit Masiri, Isabel A Del Blanco, et al.
J Agric Food Chem. 2017 Mar 1;65(8):1467-1472. doi: 10.1021/acs.jafc.6b05105. Epub 2017 Feb 14.
Gluten derived from wheat and related triticeae cereals possesses distinct amino acid sequences that provoke the immunopathogenic features of celiac disease (CD) in genetically susceptible individuals. However, the role of oat-derived gluten, or avenins, in CD pathogenesis remains a disputed matter, as evidenced by a lack in harmonized legislation regarding gluten classification in relation to gluten-free labeling. In this study, we have analyzed a panel of pure oat cultivars using a sandwich ELISA based on the R5 monoclonal antibody (mAb), which binds to canonical epitopes occurring within celiagenic peptides present in triticeae-derived gluten but reportedly not present in avenins. We have identified three varieties of oats that reproducibly bind R5 antibodies and levels indicating the presence of gluten at more than the 20 ppm gluten regulatory threshold. Nested assessment using Western blot analysis and alternative gluten detection systems corroborated these results. Collectively, these data suggest that select oat varieties may prove problematic to patients with CD and to food companies and regulatory agencies and will extend our basic understanding of current gluten detection systems.
51Adherence to Gluten-Free Diet Restores Alpha Diversity in Celiac People but the Microbiome Composition Is Different to Healthy People.PubMed
Orazio Palmieri, Stefano Castellana, Antonio Bevilacqua, et al.
Nutrients. 2022 Jun 14;14(12):2452. doi: 10.3390/nu14122452.
UNLABELLED: Celiac disease (CD) is an autoimmune disease with the destruction of small intestinal villi, which occurs in genetically predisposed individuals. At the present moment, a gluten-free diet (GFD) is the only way to restore the functionality of gut mucosa. However, there is an open debate on the effects of long-term supplementation through a GFD, because some authors report an unbalance in microbial taxa composition. METHODS: For microbiome analysis, fecal specimens were collected from 46 CD individuals in GFD for at least 2 years and 30 specimens from the healthy controls (HC). Data were analyzed using an ensemble of software packages: QIIME2, Coda-lasso, Clr-lasso, Selbal, PICRUSt2, ALDEx2, dissimilarity-overlap analysis, and dysbiosis detection tests. RESULTS: The adherence to GFD restored the alpha biodiversity of the gut microbiota in celiac people but microbial composition at beta diversity resulted as different to HC. The microbial composition of the CD subjects was decreased in a number of taxa, namely Bifidobacterium longum and several belonging to Lachnospiraceae family, whereas Bacteroides genus was found to be more abundant. Predicted metabolic pathways among the CD bacterial communities revealed an important role in tetrapyrrole biosynthesis. CONCLUSIONS: CD patients in GFD had a non-dysbiotic microbial composition for the crude alpha diversity metrics. We found significant differences in beta diversity, in certain taxon, and pathways between subjects with inactive CD in GFD and controls. Collectively, our data may suggest the development of new GFD products by modulating the gut microbiota through diet, supplements of vitamins, and the addition of specific prebiotics.
52Gluten-free diet affects fecal small non-coding RNA profiles and microbiome composition in celiac disease supporting a host-gut microbiota crosstalk.PubMed
Antonio Francavilla, Giulio Ferrero, Barbara Pardini, et al.
Gut Microbes. 2023 Jan-Dec;15(1):2172955. doi: 10.1080/19490976.2023.2172955.
Current treatment for celiac disease (CD) is adhering to a gluten-free diet (GFD), although its long-term molecular effects are still undescribed. New molecular features detectable in stool may improve and facilitate noninvasive clinical management of CD. For this purpose, fecal small non-coding RNAs (sncRNAs) and gut microbiome profiles were concomitantly explored in CD subjects in relation to strict (or not) GFD adherence over time. In this observational study, we performed small RNA and shotgun metagenomic sequencing in stool from 63 treated CD (tCD) and 3 untreated subjects as well as 66 sex- and age-matched healthy controls. tCD included 51 individuals on strict GFD and with negative transglutaminase (TG) serology (tCD-TG-) and 12 symptomatic with not strict/short-time of GFD adherence and positive TG serology (tCD-TG+). Samples from additional 40 healthy adult individuals and a cohort of 19 untreated pediatric CD subjects and 19 sex/age matched controls were analyzed to further test the outcomes. Several miRNA and microbial profiles were altered in tCD subjects (adj. p < .05). Findings were validated in the external group of adult controls. In tCD-TG-, GFD duration correlated with five miRNA levels (p < .05): for miR-4533-3p and miR-2681-3p, the longer the diet adherence, the less the expression differed from controls. tCD-TG+ and untreated pediatric CD patients showed a similar miRNA dysregulation. Immune-response, trans-membrane transport and cell death pathways were enriched in targets of identified miRNAs. , and abundances shifted (adj. p < .05) with a progressive reduction of denitrification pathways with GFD length. Integrative analysis highlighted 121 miRNA-bacterial relationships (adj. p < .05). Specific molecular patterns in stool characterize CD subjects, reflecting either the long-term GFD effects or the gut inflammatory status, in case of a not strict/short-time adherence. Our findings suggest novel host-microbial interplays and could help the discovery of biomarkers for GFD monitoring over time.
53Altered duodenal microbiota composition in celiac disease patients suffering from persistent symptoms on a long-term gluten-free diet.PubMed
Pirjo Wacklin, Pilvi Laurikka, Katri Lindfors, et al.
Am J Gastroenterol. 2014 Dec;109(12):1933-41. doi: 10.1038/ajg.2014.355. Epub 2014 Nov 18.
OBJECTIVES: A significant fraction of celiac disease patients suffer from persistent symptoms despite a long-term gluten-free diet (GFD) and normalized small bowel mucosa. The commonly suggested reasons, such as inadvertent gluten-intake or presence of other gastrointestinal disease, do not explain the symptoms in all these patients. Recently, alterations in intestinal microbiota have been associated with autoimmune disorders, including celiac disease. This led us to test a hypothesis that abnormal intestinal microbiota may be associated with persisting gastrointestinal symptoms in treated celiac disease patients. METHODS: Duodenal microbiota was analyzed in 18 GFD-treated patients suffering from persistent symptoms and 18 treated patients without symptoms by 16S rRNA gene pyrosequencing. The celiac disease patients had been following a strict GFD for several years and had restored small bowel mucosa and negative celiac autoantibodies. Their symptoms on GFD were assessed with Gastrointestinal Symptom Rating Scale. RESULTS: The results of several clustering methods showed that the treated celiac disease patients with persistent symptoms were colonized by different duodenal microbiota in comparison with patients without symptoms. The treated patients with persistent symptoms had a higher relative abundance of Proteobacteria (P=0.04) and a lower abundance of Bacteroidetes (P=0.01) and Firmicutes (P=0.05). Moreover, their microbial richness was reduced. The results indicated intestinal dysbiosis in patients with persistent symptoms even while adhering to a strict GFD. CONCLUSIONS: Our findings indicate that dysbiosis of microbiota is associated with persistent gastrointestinal symptoms in treated celiac disease patients and open new possibilities to treat this subgroup of patients.
54Metabolic syndrome in patients with coeliac disease on a gluten-free diet.PubMed
R Tortora, P Capone, G De Stefano, et al.
Aliment Pharmacol Ther. 2015 Feb;41(4):352-9. doi: 10.1111/apt.13062. Epub 2015 Jan 8.
BACKGROUND: Several studies have shown that weight changes are common in patients with coeliac disease after starting a gluten-free diet (GFD), but data on the prevalence of metabolic syndrome in this population are still scarce. AIMS: To assess the prevalence of metabolic syndrome in patients with CD at diagnosis and 1 year after starting GFD. METHODS: We enrolled all consecutive patients with newly diagnosed coeliac disease (CD) who were referred to our third-level CD Unit. For all patients we collected: waist circumference, BMI, blood pressure, lipid profile (HDL cholesterol, triglycerides) and levels of blood glucose. Diagnosis of metabolic syndrome was made according to the International Diabetes Federation (IDF) criteria for European countries. The prevalence of metabolic syndrome was re-assessed after 12 months of GFD. RESULTS: Ninety-eight patients with CD were assessed, two patients with CD (2%) fulfilled the diagnostic criteria for metabolic syndrome at diagnosis and 29 patients (29.5%) after 12 months of GFD (P < 0.01; OR: 20). With regard to metabolic syndrome sub-categories 1 year after GFD compared to baseline respectively: 72 vs. 48 patients exceeded waist circumference cut-off (P < 0.01; OR: 2.8); 18 vs. 4 patients had high blood pressure (P < 0.01; OR: 5.2); 25 vs. 7 patients exceeded glycemic threshold (P = 0.01; OR: 4.4); 34 vs. 32 patients with CD had reduced levels of HDL cholesterol (P = 0.7); and 16 vs. 7 patients had high levels of triglycerides (P = 0.05). CONCLUSIONS: Patients with coeliac disease show a high risk of metabolic syndrome 1 year after starting a gluten-free diet. We suggest that an in-depth nutritional assessment is undertaken for all patients with coeliac disease.
55"The Gluten-Free Diet and Its Relationship with Metabolic Syndrome: Dietary Friend or Foe?".PubMed
Vishal Dhruva, Christy Lawson, Caitlin Green, et al.
Curr Nutr Rep. 2021 Dec;10(4):282-287. doi: 10.1007/s13668-021-00371-3. Epub 2021 Sep 12.
PURPOSE OF REVIEW: Celiac disease (CD) is a prevalent digestive illness as well as a budding area of research in the field of gastroenterology. While investigations are underway to find new and improved pharmacological therapies for CD, the gluten-free diet (GFD) remains the only option to effectively manage the condition. RECENT FINDINGS: While the GFD is recommended for patients diagnosed with CD and other gluten-related conditions, studies show the number of individuals on the GFD surpasses the projected number of patients with these medical indications (1). The implications of widespread adoption of this dietary approach are still being determined, with many patients believing this diet will improve overall health and cardiovascular risk. This review analyzes the relationship between a GFD and metabolic syndrome in both non-celiac and celiac patients, concluding that although the diet may slightly improve overall cardiac risk factors, weight, and/or insulin resistance, its use in the absence of a gluten-related disorder is controversial.
56Obesity, Metabolic Syndrome, and Cardiovascular Risk in Gluten-Free Followers Without Celiac Disease in the United States: Results from the National Health and Nutrition Examination Survey 2009-2014.PubMed
Hyun-Seok Kim, Michael F Demyen, Justin Mathew, et al.
Dig Dis Sci. 2017 Sep;62(9):2440-2448. doi: 10.1007/s10620-017-4583-1. Epub 2017 Apr 27.
BACKGROUND: Despite unclear benefits of gluten-free diets (GFD) in the general population, gluten-free followers without medical indications are driving the market. Few studies have investigated health benefits of GFD in the general population. AIMS: To estimate metabolic and cardiovascular disease (CVD) risk profiles among gluten-free followers without celiac disease (CD). METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. There were 13,523 persons without CD who had GFD information. People with known CVD were excluded. We compared gluten-free followers without CD and the general population by selective metabolic and CVD risk profiles using survey-weighted generalized logistic regression. RESULTS: There were 155 gluten-free followers without CD and CVD, corresponding to a weighted prevalence of 1.3% (3.2 million Americans). Gluten-free followers tended to be women and have a smaller waist circumference and higher HDL cholesterol. They also had a lower BMI with a borderline p value (0.053) and significant self-reported weight loss (-1.33 kg) over one year. Moreover, gluten-free followers were more likely to consider their weight appropriate. There was no statistical difference by age, smoking, hypertension, total cholesterol, triglyceride cholesterol, HbA1c, or fasting glucose. Despite a lower probability of having metabolic syndrome (33.0 vs 38.5%) and lower 10-year CVD risk score (4.52 vs 5.70%) in gluten-free followers, there was no statistical difference. CONCLUSIONS: Although being on a GFD may be beneficial in weight management, there was no significant difference in terms of prevalence of metabolic syndrome and CVD risk score in gluten-free followers without CD.
57Newly Diagnosed Celiac Disease and Bone Health in Young Adults: A Systematic Literature Review.PubMed
Caterina Mosca, Fanney Thorsteinsdottir, Bo Abrahamsen, et al.
Calcif Tissue Int. 2022 Jun;110(6):641-648. doi: 10.1007/s00223-021-00938-w. Epub 2022 Jan 3.
Celiac disease (CD), a gluten-induced autoimmune disease, is associated with low bone mineral density (BMD) among children. Unfortunately, it is often diagnosed in adulthood, which may lead to an increased risk of fragile bones. The aim of this systematic review was to report on BMD status among young adults newly diagnosed with CD, and to examine the effect of a gluten-free diet (GFD), nutritional supplements, such as vitamin D, or antiresorptive medications on BMD recovery. Databases searched were Medline, Embase, and Cochrane Library up to July 2nd, 2020. Both observational studies and clinical trials were considered, if patients were newly diagnosed and between 20 and 35 years of age and reported on BMD. We critically appraised the identified studies using ROBINS-I and summarized the findings narratively. Out of 3991 references, we identified 3 eligible studies: one cross-sectional study and two longitudinal studies. In total, 188 patients were included, and the study population consisted primarily of women with an age range between 29 and 37 years old. Compared to healthy controls, our target population had lower BMD. Moreover, a strict GFD may increase BMD during a follow-up period of up to 5 years. Newly diagnosed CD patients aged 20-35 years are at risk of lower BMD. Therefore, it may be crucial to assess BMD at time of diagnosis in young women. Whether the results can be extrapolated to young men is unknown. While strict GFD may improve BMD over time, there is a lack of robust evidence to demonstrate that nutritional supplements or antiresorptive agents are beneficial in the prevention of fragile bones in this age group.
58Impaired Bone Microarchitecture Improves After One Year On Gluten-Free Diet: A Prospective Longitudinal HRpQCT Study in Women With Celiac Disease.PubMed
María Belén Zanchetta, Vanesa Longobardi, Florencia Costa, et al.
J Bone Miner Res. 2017 Jan;32(1):135-142. doi: 10.1002/jbmr.2922. Epub 2016 Oct 3.
We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high-resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten-free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone-specific parameters and CD serology) at both time points. Secondary, we compared 1-year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Compared with baseline, the trabecular compartment in the distal radius and tibia improved significantly (trabecular density, trabecular/bone volume fraction [BV/TV] [p < 0.0001], and trabecular thickness [p = 0.0004]). Trabecular number remained stable in both regions. Cortical density increased only in the tibia (p = 0.0004). Cortical thickness decreased significantly in both sites (radius: p = 0.03; tibia: p = 0.05). DXA increased in all regions (lumbar spine [LS], p = 0.01; femoral neck [FN], p = 0.009; ultradistal [UD] radius, p = 0.001). Most parameters continued to be significantly lower than those of healthy controls. This prospective HRpQCT study showed that most trabecular parameters altered at CD diagnosis improved significantly by specific treatment (GFD) and calcium and vitamin D supplementation. However, there were still significant differences with a control group of women of similar age and BMI. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture attains levels expected for their age. © 2016 American Society for Bone and Mineral Research.
59Accumulation of Heavy Metals in People on a Gluten-Free Diet.PubMed
Stephanie L Raehsler, Rok Seon Choung, Eric V Marietta, et al.
Clin Gastroenterol Hepatol. 2018 Feb;16(2):244-251. doi: 10.1016/j.cgh.2017.01.034. Epub 2017 Feb 20.
BACKGROUND & AIMS: Specific foods such as fish and rice have high concentrations of metals such as arsenic, mercury, lead, cadmium, and cobalt. Many gluten-free diets (GFDs) include these foods, so we evaluated whether a GFD was associated with increased metal bioaccumulation. METHODS: We performed a population-based, cross-sectional study using data collected from the National Health and Nutrition Examination Survey (NHANES), from 2009 through 2012, collecting information on the diagnosis of celiac disease and adherence to a GFD. We tested NHANES blood samples to identify individuals with undiagnosed celiac disease, using assays for immunoglobulin A tissue transglutaminase followed by a confirmatory test for endomysial antibody. Among a total of 11,354 NHANES participants, celiac disease was diagnosed in 55 participants, based on test results or a reported clinical diagnosis. We collected NHANES survey data on blood levels of lead, mercury, and cadmium from subjects who were on a GFD (n = 115) and participants who were not on a GFD (n = 11,239). Levels of total arsenic in urine samples were available from 3901 subjects not following a GFD and 32 individuals following a GFD. NHANES participants were asked questions about fish and shellfish consumption. We performed multivariate logistic regression analyses to associate gluten-related conditions with blood concentrations of mercury, cadmium, and lead and urine concentration of total arsenic, adjusting for demographic characteristics, as well as for rice consumption or seafood intake. Geometric means were reported for urinary concentrations of total arsenic and blood concentrations of mercury, cadmium, and lead for demographic groups and subjects with gluten-related conditions (subjects without celiac disease who avoid gluten). RESULTS: Persons following a GFD had significantly increased total blood mercury levels (1.37 mcg/L) compared with persons not on a GFD (0.93 mcg/L) (P = .008), as well as increased blood levels of lead (1.42 vs 1.13 mcg/L; P = .007) and cadmium (0.42 vs 0.34 mcg/L; P = .03). Urine samples from subjects on a GFD had higher concentrations of total arsenic (15.15 mcg/L) than urine samples from subjects not on a GFD (8.38 mcg/L) (P = .002). After controlling for demographic characteristics, levels of all heavy metals remained significantly higher in persons following a GFD, compared with those not following a GFD. After exclusion of persons with celiac disease, people without celiac disease on a GFD (n = 101) had significantly increased blood concentrations of total mercury (1.40 mcg/L) than persons without celiac disease and not on a GFD (n = 10,890) (0.93 mcg/L; P = .02) and higher blood concentrations of lead (1.44 vs 1.13 mcg/L; P = .01) and higher urine concentrations of total arsenic (14.69 mcg/L [n = 3632] vs 8.32 mcg/L [n = 28]; P = .01). Blood samples from persons without celiac disease avoiding gluten had higher levels of cadmium (0.42 mcg/L) than persons without celiac disease and not following a GFD (0.34 mcg/L), but this difference was not significant (P = .06). CONCLUSIONS: In an analysis of data collected from NHANES, persons on a GFD had significantly higher urine levels of total arsenic and blood levels of mercury, lead, and cadmium than persons not avoiding gluten. Studies are needed to determine the long-term effects of accumulation of these elements in persons on a GFD.
60Children With Celiac Disease Consume Specific Food Additives More Frequently Compared to Children Without Celiac Disease.PubMed
Erin McDonnell, Johanna W Lampe, Mason Nuding, et al.
Dig Dis Sci. 2023 May;68(5):1944-1949. doi: 10.1007/s10620-022-07792-2. Epub 2022 Dec 30.
BACKGROUND: Gluten-free foods often contain food additives to improve palatability, but the long-term effects on the human gastrointestinal tract are not well known. AIMS: This study aimed to quantify frequency of food additive exposure in children with and without celiac disease (CD). METHODS: Children with and without CD were enrolled and demographic data and three-day diet records were obtained. Foods were classified as gluten-free products (GFP) and "processed food", and were evaluated for presence of select food additives: polysorbate 80, carboxymethylcellulose, xanthan gum, guar gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposure was described. RESULTS: Twenty-eight participants were included in final analysis. Children with CD had a higher number of daily exposures to xanthan gum (5.3 ± 3.1 vs 2.3 ± 2.4; p = 0.009), but similar exposures to the other additives. GFP contributed 29% of total calories in the GF diet. Both groups had similar intake of processed foods. Comparing GFP and gluten-containing processed foods, 68% vs. 25% contained at least one food additive of interest (p < 0.0001); in the celiac group, those with higher consumption of GFP tended to have a higher frequency of exposure to food additives (p = 0.09). CONCLUSION: A gluten-free diet and consumption of GFP may contribute to differences in food additive intake; quantifying food additive exposures and their effect on humans requires further study.
61Mucosal Healing in Celiac Disease: Villous Architecture and Immunohistochemical Features in Children on a Long-Term Gluten Free Diet.PubMed
Roberta Mandile, Mariantonia Maglio, Caterina Mosca, et al.
Nutrients. 2022 Sep 7;14(18):3696. doi: 10.3390/nu14183696.
Considerable heterogeneity exists across studies assessing intestinal mucosal recovery in celiac (CD) patients on a gluten-free diet (GFD). We aimed at investigating histological and immunohistochemical features in CD patients on a long-term GFD and to correlate them to the GFD duration. Morphometrical and immunohistochemical analysis were retrospectively performed on duodenal biopsies in three groups of children: 33 on a long-term (>2 years) GFD (GFD-group), four of which remained seropositive despite dietary adherence, 31 with villous atrophy (ACD-group) and 76 heathy, non-celiac (CTR-group). Moreover, in the GFD-group, we correlated immunohistochemical alterations to the GFD duration. The villous to crypt (V/C) ratio significantly improved after the GFD and completely normalized in all patients, becoming even higher than in the CTR-group (median value 3.2 vs. 3, p = 0.007). In parallel, the number of CD3+ and TCRγδ+ cells in the epithelium were significantly reduced in the GFD compared to ACD patients, even if they remained higher than in the CTR-group (p < 0.05). In contrast, CD25+ cells in the lamina propria significantly decreased after the GFD (p < 0.05) and become comparable to the CTR-group (p = 0.9). In the GFD-group there was no difference in the immunohistochemical parameters between seropositive and seronegative patients and alterations did not correlate to GFD length. In conclusion, a GFD is able to both restore a normal V/C ratio and reduce inflammation, but the epithelium maintains some stigmata of the disorder, such as an increased number of CD3+ and TCRγδ+ cells. These alterations persist regardless of the duration of the GFD.