Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center, University of Paris (CRESS), Bobigny, France.
French Network for Nutrition and Cancer Research (NACRe network), Jouy-en-Josas, France.
PLoS Med. 2022 Mar 24;19(3):e1003950. doi: 10.1371/journal.pmed.1003950. eCollection 2022 Mar.
The food industry uses artificial sweeteners in a wide range of foods and beverages as alternatives to added sugars, for which deleterious effects on several chronic diseases are now well established. The safety of these food additives is debated, with conflicting findings regarding their role in the aetiology of various diseases. In particular, their carcinogenicity has been suggested by several experimental studies, but robust epidemiological evidence is lacking. Thus, our objective was to investigate the associations between artificial sweetener intakes (total from all dietary sources, and most frequently consumed ones: aspartame [E951], acesulfame-K [E950], and sucralose [E955]) and cancer risk (overall and by site).
Overall, 102,865 adults from the French population-based cohort NutriNet-Santé (2009-2021) were included (median follow-up time = 7.8 years). Dietary intakes and consumption of sweeteners were obtained by repeated 24-hour dietary records including brand names of industrial products. Associations between sweeteners and cancer incidence were assessed by Cox proportional hazards models, adjusted for age, sex, education, physical activity, smoking, body mass index, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, and baseline intakes of energy, alcohol, sodium, saturated fatty acids, fibre, sugar, fruit and vegetables, whole-grain foods, and dairy products. Compared to non-consumers, higher consumers of total artificial sweeteners (i.e., above the median exposure in consumers) had higher risk of overall cancer (n = 3,358 cases, hazard ratio [HR] = 1.13 [95% CI 1.03 to 1.25], P-trend = 0.002). In particular, aspartame (HR = 1.15 [95% CI 1.03 to 1.28], P = 0.002) and acesulfame-K (HR = 1.13 [95% CI 1.01 to 1.26], P = 0.007) were associated with increased cancer risk. Higher risks were also observed for breast cancer (n = 979 cases, HR = 1.22 [95% CI 1.01 to 1.48], P = 0.036, for aspartame) and obesity-related cancers (n = 2,023 cases, HR = 1.13 [95% CI 1.00 to 1.28], P = 0.036, for total artificial sweeteners, and HR = 1.15 [95% CI 1.01 to 1.32], P = 0.026, for aspartame). Limitations of this study include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.
In this large cohort study, artificial sweeteners (especially aspartame and acesulfame-K), which are used in many food and beverage brands worldwide, were associated with increased cancer risk. These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally.
ClinicalTrials.gov NCT03335644.
食品行业在各种食品和饮料中广泛使用人工甜味剂来替代添加糖，因为添加糖对多种慢性疾病有不良影响，这一点已得到充分证实。这些食品添加剂的安全性存在争议，关于它们在各种疾病病因学中的作用存在相互矛盾的发现。特别是，一些实验研究表明它们具有致癌性，但缺乏强有力的流行病学证据。因此，我们的目的是调查人工甜味剂摄入（全部来自各种饮食来源，以及最常消费的：阿斯巴甜[E951]、乙酰磺胺酸钾[E950]和三氯蔗糖[E955]）与癌症风险（总体和部位）之间的关联。
总体而言，我们纳入了来自法国基于人群的 NutriNet-Santé 队列（2009-2021 年）的 102865 名成年人（中位随访时间=7.8 年）。通过包括工业产品品牌名称的重复 24 小时饮食记录来获取甜味剂的饮食摄入量和消费情况。通过 Cox 比例风险模型评估甜味剂与癌症发病率之间的关联，调整因素包括年龄、性别、教育程度、体力活动、吸烟状况、体重指数、身高、随访期间体重增加、糖尿病、癌症家族史、24 小时饮食记录次数、以及能量、酒精、钠、饱和脂肪酸、纤维、糖、水果和蔬菜、全谷物食品和乳制品的基线摄入量。与非消费者相比，摄入更高剂量的总人工甜味剂（即摄入超过消费者中位数的剂量）的人群患总体癌症的风险更高（n=3358 例，风险比[HR]为 1.13[95%CI 1.03 至 1.25]，P 趋势=0.002）。特别是，阿斯巴甜（HR=1.15[95%CI 1.03 至 1.28]，P=0.002）和乙酰磺胺酸钾（HR=1.13[95%CI 1.01 至 1.26]，P=0.007）与癌症风险增加相关。乳腺癌（n=979 例，HR=1.22[95%CI 1.01 至 1.48]，P=0.036，阿斯巴甜）和与肥胖相关的癌症（n=2023 例，HR=1.13[95%CI 1.00 至 1.28]，P=0.036，总人工甜味剂，HR=1.15[95%CI 1.01 至 1.32]，P=0.026，阿斯巴甜）的风险也有所增加。本研究的局限性包括潜在的选择偏倚、残余混杂和反向因果关系，但进行了敏感性分析以解决这些问题。
在这项大型队列研究中，人工甜味剂（尤其是阿斯巴甜和乙酰磺胺酸钾）在全球许多食品和饮料品牌中使用，与癌症风险增加相关。这些发现为欧洲食品安全局和其他全球卫生机构正在对食品添加剂甜味剂进行的重新评估提供了重要和新颖的见解。
ClinicalTrials.gov NCT03335644。
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