Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studiesBMJ 2019; 364 doi: https://doi.org/10.1136/bmj.k4718 (Published 02 January 2019) Cite this as: BMJ 2019;364:k4718
- Ingrid Toews, researcher1,
- Szimonetta Lohner, researcher2,
- Daniela Küllenberg de Gaudry, researcher1,
- Harriet Sommer, researcher1 3,
- Joerg J Meerpohl, codirector1 4
- 1Institute for Evidence in Medicine (for Cochrane Germany Foundation), Medical Centre of the University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 153, 79110 Freiburg, Germany
- 2Cochrane Hungary, Clinical Centre of the University of Pécs, Medical School, University of Pécs, Pécs, Hungary
- 3Institute for Medical Biometry and Statistics, Medical Centre of the University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 4Centre of Epidemiological and Statistical Research, Sorbonne Paris Cité, Inserm/Université Paris Descartes, Cochrane France, Paris, France
- Correspondence to: J J Meerpohl
- Accepted 29 October 2018
Objective To assess the association between intake of non-sugar sweeteners (NSS) and important health outcomes in generally healthy or overweight/obese adults and children.
Design Systematic review following standard Cochrane review methodology.
Data sources Medline (Ovid), Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and reference lists of relevant publications.
Eligibility criteria for selecting studies Studies including generally healthy adults or children with or without overweight or obesity were eligible. Included study designs allowed for a direct comparison of no intake or lower intake of NSS with higher NSS intake. NSSs had to be clearly named, the dose had to be within the acceptable daily intake, and the intervention duration had to be at least seven days.
Main outcome measures Body weight or body mass index, glycaemic control, oral health, eating behaviour, preference for sweet taste, cancer, cardiovascular disease, kidney disease, mood, behaviour, neurocognition, and adverse effects.
Results The search resulted in 13 941 unique records. Of 56 individual studies that provided data for this review, 35 were observational studies. In adults, evidence of very low and low certainty from a limited number of small studies indicated a small beneficial effect of NSSs on body mass index (mean difference −0.6, 95% confidence interval −1.19 to −0.01; two studies, n=174) and fasting blood glucose (−0.16 mmol/L, −0.26 to −0.06; two, n=52). Lower doses of NSSs were associated with lower weight gain (−0.09 kg, −0.13 to −0.05; one, n=17 934) compared with higher doses of NSSs (very low certainty of evidence). For all other outcomes, no differences were detected between the use and non-use of NSSs, or between different doses of NSSs. No evidence of any effect of NSSs was seen on overweight or obese adults or children actively trying to lose weight (very low to moderate certainty). In children, a smaller increase in body mass index z score was observed with NSS intake compared with sugar intake (−0.15, −0.17 to −0.12; two, n=528, moderate certainty of evidence), but no significant differences were observed in body weight (−0.60 kg, −1.33 to 0.14; two, n=467, low certainty of evidence), or between different doses of NSSs (very low to moderate certainty).
Conclusions Most health outcomes did not seem to have differences between the NSS exposed and unexposed groups. Of the few studies identified for each outcome, most had few participants, were of short duration, and their methodological and reporting quality was limited; therefore, confidence in the reported results is limited. Future studies should assess the effects of NSSs with an appropriate intervention duration. Detailed descriptions of interventions, comparators, and outcomes should be included in all reports.
Systematic review registration Prospero CRD42017047668.
Contributors: SL, IT, and JJM conceived and designed the review. JJM coordinated the review. SL, JJM, and IT designed the search strategy. SL and IT undertook the searches and screened the search results. IT organised the retrieval of the papers. SL, IT, DKdG, and JJM screened the papers against eligibility criteria. SL, IT, and DKdG appraised the quality of the papers. SL, IT, DKdG, and HS extracted data from the papers. HS analysed the data. SL, JJM, IT, and DKdG interpreted data. IT, SL, DKdG, and JJM wrote the review and its protocol. JJM, SL, and DKdG provided general advice on the review. JJM secured funding for the review. SL, JJM, and IT performed previous work that was the foundation of the current review. JJM is the guarantor of this manuscript. The questions guiding the review were discussed and developed by the WHO NUGAG Subgroup on Diet and Health, and the study protocol was approved, by the NUGAG Subgroup on Diet and Health. Neither WHO nor the WHO NUGAG Subgroup on Diet and Health played a role in data collection or analysis. All authors, external and internal, had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding: The research was funded by WHO. The research was conducted independently from the funder, and researchers are independent from the funder.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from WHO for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Ethical approval was not required for this research.
Data sharing: Full datasets can be obtained from the corresponding author at Meerpohl@cochrane.de.
The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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