Acute glycemic and insulinemic effects of low-energy sweeteners: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background It has been suggested that low-energy sweeteners (LES) may be associated with an increased risk of metabolic diseases, possibly due to stimulation of glucose-responsive mechanisms. Objective We conducted a systematic review and meta-analysis of human intervention studies examining the acute effect of LES intake on postprandial glucose (PPG) and postprandial insulin (PPI) responses, in order to comprehensively and objectively quantify these relations. Methods We systematically searched the Medline, OVID FSTA, and SCOPUS databases until January 2020. Randomized controlled trials comparing acute postprandial effects on PPG and/or PPI after exposure to LES, either alone, with a meal, or with other nutrient-containing preloads to the same intervention without LES were eligible for inclusion. PPG and PPI responses were calculated as mean incremental area under the curve divided by time. Meta-analyses were performed using random effects models with inverse variance weighing. Results Twenty-six papers (34 PPG trials and 29 PPI trials) were included. There were no reports of statistically significant differences in the effects of LES on PPG and PPI responses compared with control interventions. Pooled effects of LES intake on the mean change difference in PPG and PPI were −0.02 mmol/L (95% CI: −0.09, 0.05) and −2.39 pmol/L (95% CI: −11.83, 7.05), respectively. The results did not appreciably differ by the type or dose of LES consumed, cointervention type, or fasting glucose and insulin levels. Among patients with type 2 diabetes, the mean change difference indicated a smaller PPG response after exposure to LES compared with the control (−0.3 mmol/L; 95% CI: −0.53, −0.07). Conclusions Ingestion of LES, administered alone or in combination with a nutrient-containing preload, has no acute effects on the mean change in postprandial glycemic or insulinemic responses compared with a control intervention. Apart from a small beneficial effect on PPG (−0.3 mmol/L) in studies enrolling patients with type 2 diabetes, the effects did not differ by type or dose of LES, or fasting glucose or insulin levels. This review and meta-analysis was registered at PROSPERO as CRD42018099608.

Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose‐ranging study

“…A number of studies indicate that sweeteners-whether calorific or non-calorific-can influence glycaemic control both positively and negatively. 40,41 Animal studies conducted with erythritol showed that, when given over a longer period, erythritol exerts antihyperglycaemic effects, possibly by enhancing insulin-mediated glucose uptake and reducing intestinal glucose absorption in diabetic rats. 42 Another important player in glycaemic control is the pancreatic hormone glucagon-a hormone produced in the α-cells of the pancreatic isletswhich stimulates hepatic glycogenolysis and gluconeogenesis in hypoglycaemic states to restore glucose homeostasis, and in this way counterbalances insulin.…”

Low-calorie sweeteners in the human diet: scientific evidence, recommendations, challenges and future needs. A symposium report from the FENS 2019 conference

“…Professor Raben took the opportunity to present some preliminary results from a systematic review and meta-analysis of human intervention studies. It examined the acute effect of LCS intake on PPG and PPI responses and found that the ingestion of LCS has no acute effects on the mean change in postprandial glycemic or insulinemic responses compared with a control intervention (34) .…”

Is There an Academic Bias against Low-Energy Sweeteners?

“…Given this extensive literature on mechanisms, one might expect that there is an equally large and convincing body of evidence demonstrating the adverse effects of LES on humans, prompting the need for mechanistic understanding and explanations. Yet, every recent systematic review (SR) and meta-analysis of randomised controlled trials (RCTs) in humans—from acute studies of appetite and glycaemic responses through longer-term studies with anthropometric and glycaemic control endpoints—finds neutral or beneficial effects of LES, and almost no indications of adverse effects on these outcomes [ 2 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Thus, the stream of papers offering a multitude of mechanisms for the adverse effects of LES exists within the context of a wall of empirical evidence that fails to find any adverse effects to be explained.…”

“…Despite a number of significant shortcomings in that research [ 22 , 23 ], this single paper set off a stampede of research funding and activity on LES and the microbiota, and left much of the scientific community presuming that the original premise was simply true. Yet, the supposedly explained phenomenon (i.e., LES producing impaired glycaemic control) has no empirical support from comprehensive systematic reviews of the evidence [ 9 , 13 , 14 , 17 , 18 , 24 , 25 ]. This fact by itself should render the supposed “mechanism” specious, while years of subsequent research have also left doubt on the replicability of the initial research and basic premise that LES cause important, pathological changes in the gut microbiota [ 12 , 19 , 23 , 26 ].…”