Artificial sweeteners: Too sweet to be true?

By Naveed Saleh, MD, MS, for MDLinx
Published November 25, 2019

Key Takeaways

More than 100 years ago, non-caloric artificial sweeteners were discovered, and American diets were forever changed. Today, an estimated 32% of American adults consume artificial sweeteners, and the number of products that contain artificial sweeteners is increasing.

Although concerns have been raised, artificial sweeteners have proven to be safe. The FDA has greenlighted high-intensity artificial sweeteners—including acesulfame potassium, neotame, saccharin, sucralose, and aspartame—as well as natural sweeteners, such as plant-derived stevia and monk fruit extract.

Although many physicians recommend that their patients use artificial sweeteners to curb calorie intake and help with control blood sugars, some researchers have shown—counterintuitively—that artificial sweeteners may actually exacerbate conditions of metabolic syndrome, including weight gain, cardiovascular disease, and type 2 diabetes.

So, what’s the low-down on no-calorie artificial sweeteners?

Types of sweeteners

In the United States, there are currently more than 6,000 food items on the market that contain artificial sweeteners.

The oldest artificial sweetener is saccharin, which was formulated at Johns Hopkins University in 1879. Saccharin is between 200 and 700 times sweeter than table sugar (sucrose), and is found in soft drinks, candy, gum, salad dressings, toothpaste, medications, and mouthwash.

Aspartame is an example of a second-generation artificial sweetener, and is about 200 times sweeter than sucrose. Acesulfame potassium and sucralose are about 200 and 600 times sweeter than sucrose, respectively.

Stevia is a newer artificial sweetener derived from the leaves of plants. Sorbitol and xylitol are also newer additions, and are made from fermented sugar alcohols. When consumed in large quantities, both sorbitol and xylitol can result in diarrhea.


Mechanisms underlying the counterintuitive effects of artificial sweeteners could include the following:

  • Increased appetite

  • Impaired insulin response

  • Failure of the body to respond to real sugar

  • Stimulation of intestinal sugar uptake

Nevertheless, artificial sweeteners have been shown to be effective at controlling weight in some studies. However, such studies compared the intake of artificial sweeteners with caloric sweeteners; few studies have compared artificial sweetener intake with avoidance of sweeteners altogether or with intake of natural sweeteners.

To make things even more nebulous, reverse causality could be at play in the biologic effects of artificial sweeteners. In other words, the consumption of artificial sweeteners could result in metabolic derangements. Alternatively, those who are overweight or hypertensive may be drawn to the consumption of artificial sweeteners.

Metabolic syndrome

Let’s take a look at two different studies that examined the near- and long-term effects of artificial sweeteners on metabolic syndrome and diabetes:

In the first—a low-power study of short-term changes in biomarkers—normoglycemic participants consumed pure forms of sucralose and aspartame daily for 2 weeks. Outcomes examined included serum glucose levels, insulin levels, glucagon-like peptide-1 (GLP-1), and leptin. The researchers observed no effect of these artificial sweeteners on biomarkers. Interestingly, other researchers have indicated that acute doses of these artificial sweeteners negatively influence insulin and blood glucose levels.

With regard to long-term effects, researchers of the Multi-Ethnic Study of Atherosclerosis followed 6,814 Caucasian, African American, Hispanic, and Chinese adults aged 45-84 years for subclinical cardiovascular disease. They found that daily diet soda intake resulted in a 67% increase in the relative risk of type diabetes and a 36% increase in the relative risk of metabolic syndrome compared with abstinence.


In a review article published in Current Gastroenterology Reports, researchers delineated how artificial sweeteners affect weight gain, noting that:

“[Artificial sweeteners] activate the oral taste receptors, only partially activate the food reward pathway, and fail to activate the post-ingestion pathway because of the lack of caloric energy. Changes in these pathways ultimately lead to increased appetite, increased food craving, and greater caloric consumption.”


In a nutrition study highlighted in Gut Microbes, investigators assessed microbiome composition and metabolic outcomes in 381 participants without diabetes.

They demonstrated that artificial sweetener intake was related to detrimental changes in BMI, hemoglobin A1c, fasting glucose levels, and blood pressure levels. They also showed that artificial sweeteners altered the gut microbiome in ways that reduced glycemic response. Specifically, they observed augmentation in the Actinobacteria phylum, the Enterobacteriales order, and several taxa from the Clostridiales order.

“This suggests that the gut microbiome composition of an individual may be indicative of his susceptibility and personalized response to [non-caloric artificial sweeteners] or other food related compounds,” the authors wrote. “Thus, this serves as a special case of ‘personalized nutrition’ and suggests that the microbiome should be considered an important ‘player’ when attempting to design individually tailored health-maintaining diets.”

The verdict?

Although artificial sweeteners have been around for a long time, we still don’t understand their seemingly ineffable effects. Looking forward, prospective examination of the long-term effects of artificial sweeteners is necessary. Furthermore, it may be a good idea to focus on the effects of artificial sweeteners on the microbiome, because these changes likely affect absorption and glucose metabolism. Finally, some experts suggest that plant-based sweeteners may be a healthier option and should be further researched.

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