Metabolic effects of aspartame in adulthood: a systematic review and meta-analysis of randomized clinical trials

<b>Background</b>: Data about harms or benefits associated with the consumption of aspartame, a non-nutritive sweetener worldwide consumed, is still controversial. This systematic review and meta-analysis of randomized controlled clinical trials aimed to assess the effect of aspartame consumption on metabolic parameters related to diabetes and obesity. <b>Methods</b>: The search was performed on Cochrane, LILACS, PubMed, SCOPUS, Web of Science databases and on a grey literature using Open Grey, Google Scholar and ProQuest Dissertations &amp; Theses Global. Searches across all databases were conducted from the earliest available date up to April 13, 2016, without date and language restrictions. Pooled mean differences were calculated using a random or fixed-effects model for heterogeneous and homogenous studies, respectively. <b>Results</b>: Twenty nine articles were included in qualitative synthesis and twelve, presenting numeric results, were used in meta-analysis. Fasting blood glucose (mmol/L), insulin levels (μU/mL), total cholesterol (mmol/L), triglycerides concentrations (mmol/L), high-density lipoprotein cholesterol (mmol/L), body weight (Kg) and energy intake (MJ) were considered as the main outcomes in subjects that consumed aspartame and results were presented as (mean difference; % Confidence Interval, range). Aspartame consumption was not associated with alterations on blood glucose levels compared to control (−0.03 mmol/L; 95% CI, −0.21 to 0.14) or to sucrose (0.31 mmol/L; 95% CI, −0.05 to 0.67) and on insulin levels compared to control (0.13 μU/mL; 95% CI, −0.69 to 0.95) or to sucrose (2.54 μU/mL; 95% CI, −6.29 to 11.37). Total cholesterol was not affected by aspartame consumption compared to control (−0.02 mmol/L; 95% CI, −0.31 to 0.27) or to sucrose (−0.24 mmol/L; 95% CI, −0.89 to 0.42). Triglycerides concentrations were not affected by aspartame consumption compared to control (0.00 mmol/L; 95% CI, −0.04 to 0.05) or to sucrose (0.00 mmol/L; 95% CI, −0.09 to 0.09). High-density lipoprotein cholesterol serum levels were higher on aspartame compared to control (−0.03 mmol/L; 95% CI, −0.06 to −0.01) and lower on aspartame compared to sucrose (0.05 mmol/L; 95% CI, 0.02 to 0.09). Body weight did not change after aspartame consumption compared to control (5.00 Kg; 95% CI, −1.56 to 11.56) or to sucrose (3.78 Kg; 95% CI, −2.18 to 9.74). Energy intake was not altered by aspartame consumption compared to control (−0.49 MJ; 95% CI, −1.21 to 0.22) or to sucrose (−0.17 MJ; 95% CI, −2.03 to 1.69). <b>Conclusions</b>: Data concerning effects of aspartame on main metabolic variables associated to diabetes and obesity do not support a beneficial related to its consumption.**背景**：全球范围内广泛应用的非营养性甜味剂阿斯巴甜（aspartame）的摄入相关利弊数据仍存在争议。本项针对随机对照临床试验的系统综述与荟萃分析，旨在评估阿斯巴甜摄入对与糖尿病及肥胖相关的代谢参数的影响。**方法**：检索范围涵盖Cochrane、LILACS、PubMed、SCOPUS、Web of Science数据库，以及Open Grey、Google Scholar、ProQuest Dissertations & Theses Global（博硕士学位论文全球数据库）等灰色文献资源。所有数据库的检索时限均为自建库至2016年4月13日，未设置日期与语言限制。针对异质性研究与同质性研究，分别采用随机效应模型与固定效应模型计算合并均数差。**结果**：最终纳入29篇文献进行定性综合，其中12篇提供量化数据的文献被用于荟萃分析。本研究的主要结局指标包括受试人群的空腹血糖（单位：mmol/L）、胰岛素水平（单位：μU/mL）、总胆固醇（单位：mmol/L）、甘油三酯浓度（单位：mmol/L）、高密度脂蛋白胆固醇（单位：mmol/L）、体质量（单位：Kg）及能量摄入（单位：MJ），研究结果以「均数差；95%置信区间，取值范围」的形式呈现。与对照组相比，阿斯巴甜摄入未对血糖水平产生显著影响（均数差：-0.03 mmol/L；95%置信区间：-0.21~0.14）；与蔗糖组相比，结果同样无统计学差异（均数差：0.31 mmol/L；95%置信区间：-0.05~0.67）。胰岛素水平方面，与对照组相比（均数差：0.13 μU/mL；95%置信区间：-0.69~0.95）或与蔗糖组相比（均数差：2.54 μU/mL；95%置信区间：-6.29~11.37），均未出现显著改变。与对照组相比，阿斯巴甜摄入未对总胆固醇水平产生影响（均数差：-0.02 mmol/L；95%置信区间：-0.31~0.27）；与蔗糖组相比，结果亦无显著差异（均数差：-0.24 mmol/L；95%置信区间：-0.89~0.42）。甘油三酯浓度方面，与对照组相比（均数差：0.00 mmol/L；95%置信区间：-0.04~0.05）或与蔗糖组相比（均数差：0.00 mmol/L；95%置信区间：-0.09~0.09），均未受阿斯巴甜摄入的影响。高密度脂蛋白胆固醇血清水平方面，阿斯巴甜组较对照组更高（均数差：-0.03 mmol/L；95%置信区间：-0.06~-0.01），而较蔗糖组更低（均数差：0.05 mmol/L；95%置信区间：0.02~0.09）。体质量方面，与对照组相比（均数差：5.00 Kg；95%置信区间：-1.56~11.56）或与蔗糖组相比（均数差：3.78 Kg；95%置信区间：-2.18~9.74），阿斯巴甜摄入后体质量未发生显著变化。能量摄入方面，与对照组相比（均数差：-0.49 MJ；95%置信区间：-1.21~0.22）或与蔗糖组相比（均数差：-0.17 MJ；95%置信区间：-2.03~1.69），均未因阿斯巴甜摄入而出现显著改变。**结论**：现有关于阿斯巴甜对与糖尿病及肥胖相关的主要代谢变量的影响的数据，并不支持其摄入具有有益作用。