Study probes the hidden impact of low-cal sweeteners on gut health

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A recent study published in the journal nutrition The available evidence on the effects of low- and non-caloric sweeteners (LNCSs) on the gut microbiota is reviewed.

High rates of obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease have become a significant public health concern. Increased sugar intake has been identified as a cause of these disorders, leading to the introduction of non-nutritive sweeteners (NNSs). Alternative sweeteners contain no or low calories and their consumption has increased significantly over time. It has been reported that 40% of adults in the United States (US) consumed alternative sweeteners between 2009 and 2012, an increase of 54% from estimates in 1999 and 2000.

Study: Effects of low- and non-caloric sweeteners on gut microbiota: review of clinical trials and cross-sectional studies

Study: Effects of low- and non-caloric sweeteners on the gut microbiota: a review of clinical trials and cross-sectional studies.

Whether or not sweeteners have any harmful effects is still debated. Some studies report links between consumption of alternative sweeteners and changes in physiological parameters such as insulin resistance (IR) and glucose tolerance, implicating gut microbiota in mediating these effects. Further, studies have demonstrated associations between low gut microbial richness and increased IR, dyslipidemia, adiposity, and inflammation. Dietary patterns can modulate the gut microbiota, thus influencing physiological factors associated with metabolic disease.

Research and results

In the current study, researchers analyzed the current evidence for the effects of LNCS on the gut microbiota. PubMed and Ovid databases were searched for cross-sectional studies and clinical trials. Only studies with healthy populations were selected. Studies that assessed oral microbiota were excluded. The initial search yielded 465 records; After duplicate screening and exclusion, the full text of 14 articles was reviewed. Overall, 11 studies – four cross-sectional studies and eight clinical trials – were included for analysis.

One study included both cross-sectional and clinical trial protocols. Six trials were randomized controlled trials; One was a non-randomized uncontrolled trial, and one was a randomized uncontrolled trial. The study was conducted between 2006 and 2022 in the United States, United Kingdom (UK), Europe, Israel, Canada and Chile. Two experiments evaluated the effect of saccharin on gut microbiota; One investigated sucralose, three tested polyols, and two studied multiple NNS.

Two cross-sectional studies evaluated the relationship between artificially sweetened beverages (ASB) and microbiota composition; One study focused on consumption of aspartame and acesulfame, while another assessed global consumption of artificial sweeteners. One trial found no effect of supplementing 800 mg of saccharin for 46 people for two weeks. In contrast, other experiments have noted that microbiota cluster differently in individuals with poor glycemic response compared to those with normal glycemic response.

Another study found no change in gut microbiota after sucralose supplementation. Meanwhile, a two-week sucralose supplement changed the gut microbiota in a different study, increasing it Doria longicatena And Eubacterium. Similarly, the aspartame trial did not observe changes in gut microbiota after a two-week intervention. Studies investigating polyols (isomalt, lactitol and maltitol) have revealed their beneficial effects on the gut microbiota.

In particular, consumption of these polyols significantly increased bifidobacterial populations. A cross-sectional study identified differences in microbial diversity between consumers of acesulfame-K or aspartame and non-consumers. Also, a positive association was reported between artificial sweeteners and numerous taxonomic entities such as Actinomycetota, Enterobacteriaceae and Deltaproteobacteria.

A Swedish study examined consumption of ASB or naturally sweetened beverages in 1,085 healthy adults and found no association between ASB consumption and microbiota changes. Further, a Canadian study analyzing ASB intake among children and their mothers found that maternal ASB intake was associated with a decrease in its intake. Bacteroidetes spp In a study in children, sucralose and saccharin supplementation attenuated participants’ glycemic response.

Germ-free mice receiving microbiomes from participants with impaired glucose tolerance (responders) developed an enhanced glycemic response compared to those receiving microbiomes from non-responders. A few experiments suggested that the glycemic response to NNS was partially driven by baseline interindividual differences in gut microbiota. Notably, individual baseline microbiota compositions of individuals with elevated post-intervention insulinemia were independent of placebo or sucralose intake.


In summary, two clinical trials suggested that NNSs altered the gut microbiota and revealed a causal effect between sucralose or saccharin intake and glucose tolerance in rats. Experiments on polyols have suggested beneficial effects on microbiota. A few cross-sectional studies have reported associations between the use of alternative sweeteners and changes in harmful gut microbiota.

Furthermore, baseline microbiota composition may modulate glycemic and microbial responses to LNCs. Variation in findings across studies may be attributed to small sample sizes, methodological differences, short/varied intervention durations, and individual responses to LNCSs. Overall, larger cohort studies with more realistic sweetener doses and longer durations are needed to support these findings.

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