The Not-So-Sweet Health Impacts of Artificial Sweeteners

History of Artificial Sweeteners 

After the discovery of the first artificial sweetener, saccharin, in 1879, industrial foodways introduced artificial sweeteners, or ‘non-nutritive sweeteners,’ in the late 1800s. Since the introduction of artificial sweeteners into the food industry in the United States in the 1950s, their consumption has increased rapidly, with products mostly marketed for the management of diabetes and weight loss.1

In the United States, there are 8 approved artificial sweeteners, two of which are considered to be naturally derived. The naturally derived sweeteners include stevia and monk fruit (Luo Han Guo) extract. The synthetic sweeteners include aspartame, acesulfame potassium, neotame, saccharin, sucralose, and advantame. 1,2

Metabolism of Artificial Sweeteners

Originally, it was thought that these non-nutritive sweeteners were not metabolized by the body after ingestion. However, studies show that gut bacteria metabolize many of these sweeteners, ultimately altering the gut microbiome.

Saccharin, for example, is absorbed in the small intestine and can modulate the gut microbiome through its bacteriostatic properties, as observed in animal studies. This bacteriostatic mechanism likely contributes to alterations in the gut microbiome by harming beneficial microorganisms. Saccharin has also been shown to encourage the growth of pro-inflammatory microorganisms within the gut. Saccharin-dependent dysbiosis has been connected to alterations in glucose tolerance, showing a connection between the disrupted microbiome and metabolic health. 

As another example, sucralose has been shown to alter the gut microbiome and promote dysbiosis in human, animal, and in vivo studies. It is also thought that sucralose may increase Escherichia coli antimicrobial resistance and may increase mutation frequency, making the bacteria more difficult to manage.1,2

Effects of Artificial Sweeteners

Microbiome

Animal studies have shown that artificial sweeteners alter short-chain fatty acid synthesis, potentially increasing gut inflammation. These short-chain fatty acids are essential for lipid and glucose metabolism, and disruptions in SCFAs contribute to glucose intolerance, elevated LDL, and low HDL levels.1 

While we know that there is a connection between artificial sweeteners and alterations in the gut microbiome, we do not know the full mechanism underlying these alterations. It is possible that artificial sweeteners induce the secretion of defensins, proteins that modulate the gut microbiome. Observations also show that Caco-2 cells lining the intestine are highly susceptible to artificial sweeteners, and that saccharin, sucralose, and aspartame increase biofilm formation in the intestine. Biofilms serve a purpose in the gastrointestinal tract, but under stress or illness, pathogenic microorganisms can form biofilms that override the normal ones, leading to further dysbiosis. Due to their composition, these biofilms are difficult to eradicate and manage. They are often resistant to antimicrobials and are associated with gastrointestinal conditions such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and small intestinal bacterial overgrowth (SIBO).1 

Metabolic

Multiple animal studies have shown that saccharin is hepatotoxic, with short-term exposure leading to elevated liver enzyme levels. Studies show that long-term aspartame consumption can result in liver fibrosis and degeneration. This is likely due to increased oxidative stress resulting from methanol produced as a byproduct of aspartame consumption. 

Within a healthy digestive system, bacteria in the colon produce bile acids, which increase the absorption of fat-soluble vitamins and help maintain healthy cholesterol levels. While many studies have shown that artificial sweeteners alter bile acid metabolism, sucralose specifically has shown an increase in hepatic cholesterol levels in rodent studies. 

The Women’s Health Initiative Observational Study revealed that high intake of artificial sweeteners (2 or more 12-ounce beverages containing artificial sweeteners) is associated with an increased risk of ischemic stroke, heart disease, and all-cause mortality.3

While these artificial sweeteners may support weight management and glycemic control in certain patients, there are challenges to consider: they may ultimately cause unintended damage to the gut microbiome, unintended metabolic consequences, and an increased risk of cardiovascular disease and ischemic stroke. While the intended benefits of artificial sweeteners are to provide a low-calorie option to appeal to the sweet tooth, the not-so-sweet health impacts of artificial sweeteners are too great to ignore. 

Looking for sweetener alternatives? Check out this blog to find out some alternatives we suggest to curb that sweet tooth while avoiding artificial choices: Sweeteners for cooking.

References

1. Basson AR, Rodriguez-Palacios A, Cominelli F. Artificial Sweeteners: History and New Concepts on Inflammation. Front Nutr. 2021;8:746247. Published 2021 Sep 24. doi:10.3389/fnut.2021.746247
2. M M, Vellapandian C. Exploring the Long-Term Effect of Artificial Sweeteners on Metabolic Health. Cureus. 2024;16(9):e70043. Published 2024 Sep 23. doi:10.7759/cureus.70043 
3. Mossavar-Rahmani Y, Kamensky V, Manson JE, et al. Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women’s Health Initiative. Stroke. 2019;50(3):555-562. doi:10.1161/STROKEAHA.118.023100