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Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies

BMJ 2019; 364 doi: (Published 02 January 2019) Cite this as: BMJ 2019;364:k4718

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Non-sugar sweeteners and health

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Non-sugar sweeteners: lack of evidence that they help to control weight

Re: Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies

In this comprehensive systematic review and meta-analysis, Toews et al. determine if definitive conclusions can be drawn regarding the effects of non-sugar sweeteners (NSSs) on multiple health parameters. From a weight management perspective, the utility of NSSs has been a longstanding controversy that began with early epidemiological studies showing direct correlations between the usage of low-calorie sweeteners and obesity [1]. On one hand, this relationship may indicate successful usage by a population in need, and on the other hand, it may suggest that NSSs exacerbate weight gain. Just as with any question of association vs. causation, we look to randomized controlled trials (RCTs) and basic science mechanisms for answers.

The authors separately analyzed the data from RCTs but were unable to draw strong conclusions on NSS’s effect on weight as the RCTs were few in number with small sample sizes and short durations. Furthermore, there are limited RCTs per individual NSS. Given that each NSS may affect normal physiology differently in terms of glucose homeostasis and the microbiome [2], it is unsurprising that we continue to find conflicting results when studies are pooled or compared.

For example, in this meta-analysis, 2 of the 2 RCTs that used aspartame in adults with obesity showed significant weight loss, while 1 RCT showed no weight loss with stevia. Prior studies [3] have shown aspartame to have no effect on glucose homeostasis, while stevia induced lower plasma glucose and insulin concentrations. Saccharin, which was among the first to be implicated in worsening glucose intolerance [4], was found to be associated with a higher glucose level in children as compared to sucrose but this was in a non-randomized RCT.

The discrepancy between inconclusive meta-analyses and the direct association between NSS and obesity remains unresolved. In addition to limitations set forth by Toews et al., it is notable too that NSSs are often tested in isolation but are rarely consumed in isolation. There are few studies that test NSSs concurrently with a mixed meal [5] or glucose load [6]. A systematic review focusing on these alone may form a clearer picture and provide conclusions that are more applicable to real-world use.

For now, counseling patients on the relative health effects of their consumption choices may be most realistic. Oftentimes patients transition themselves from regular soda to diet soda to flavored seltzer to water in their journey towards weight loss and health.

[1] Sylvetsky AC, et al. Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr. 2012 Sep;96(3):640-6
[2] Suez J, et al. Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes. 2015;6(2):149-55.
[3] Romo-Romo A, et al. Effects of the Non-Nutritive Sweeteners on Glucose Metabolism and Appetite Regulating Hormones: Systematic Review of Observational Prospective Studies and Clinical Trials. PLoS One. 2016 Aug 18;11(8):e0161264.
[4] Suez J, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6.
[5] Gregersen S, et al. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism. 2004 Jan;53(1):73-6.
[6] Bryant CE, et al. Non-nutritive sweeteners: no class effect on the glycemic or appetite responses to ingested glucose. Eur J Clin Nutr. 2014 May; 68(5): 629–631.

Competing interests: No competing interests

04 March 2019
Beverly G Tchang
Weill Cornell Medical College
New York, NY