Writer: Jamie Saito '25
Editor: Surya Khatri '24
Image Credit: The Difference Between Sucrose and Sucralose https://www.thoughtco.com/difference-between-sucrose-and-sucralose-607389
As the prevalence of diabetes and obesity has increased in recent decades, scientists have emphasized the importance of reducing added-sugar consumption. In response, the food industry has placed an increased emphasis on the addition of nonnutritive sweeteners into a variety of foods. While artificial sweeteners originally found their home in sugar sweetened beverages, their presence has expanded to a wide variety of pantry items, including products such as bread, yogurt, muffins, and salad dressings (1).
Nonnutritive sweeteners (NNS), or sugar substitutes, are chemically synthesized substances that mimic the taste of sugar. These sweeteners are much sweeter than normal table sugar, or sucrose, so they are used in very small amounts to achieve the same effect (2). Currently, there are six NNS approved by the FDA: saccharin (Sweet’n’Low), sucralose (Splenda), aspartame (Nutra Sweet; Equal), acesulfame potassium (Ace K; Sunette; Sweet & Safe; SweetOne), neotame, and advantame (3). Though these alternatives were initially proposed as non-invasive and healthy choices, recent studies suggest that a more sinister physiological response may increase the risk of obesity, diabetes, and heart disease. Since NNS are relatively new in the food industry, their long term effects on human health still remain largely unknown.
Initial animal studies suggest that NNS may actually lead to overeating. In an early 2011 study, scientists studied the caloric outcomes of rats exposed to non-caloric sweeteners. After administering glucose, polycose, and saccharin diets, the researchers studied two sequential effects. First, they discovered that exposure to saccharin weakened the rats’ postingestive caloric outcomes. Second, they found that the rats who consumed saccharin produced greater caloric intake and increased in body weight (4). Usually, the ingestion of glucose is linked to hormonal and metabolic responses that promote the uptake of the high energy food. However, this experiment suggests that NNS may decrease these metabolic effects, which may result in increased body mass.
However, similar human studies are less conclusive, suggesting that more complex physiological pathways may be at play. In a 2012 study focusing on the brain’s reward system after sugar consumption, scientists found that participants who regularly consumed diet sodas had an altered response to a sweet taste (5). Using function MRIs, the researchers tracked which parts of the brain were activated after consumption of a sweetened drink. Participants who consumed diet sodas—and therefore consumed artificial sweeteners—on a regular basis showed less activation of the caudate head, a specific portion of the brain. Previous research hypothesized that the caudate head may not only be associated with food motivation but that decreased activity of this portion may be linked to obesity (5). Therefore, while these results do not provide us with the entire picture, preliminary evidence suggests that NNS may influence the brain’s response to sugar consumption.
Additionally, seven studies reviewed by scientists at the University of Manitoba in 2017 provide a bigger picture of the long term effects of NNS consumption. Looking at the outcome of 1003 people followed for an average of 6 months, researchers concluded that NNS did not show a consistent link with weight loss. Instead, there seemed to be a long-term increased risk of weight gain, obesity, high blood pressure, diabetes, and heart disease (6). While these findings seem to corroborate the fact that artificial sweeteners may be linked to deleterious effects, the pathophysiology of these responses still remains unclear.
One proposed answer to this question suggests that alterations in the gut microbiome may lead to increased glucose intolerance. In a recent study done in 2022, participants who normally did not consume NNS containing foods were exposed to an altered diet for 14 days. Researchers then monitored the glycemic response of these individuals using glucose monitors, glucose tolerance tests, and microbiome samples. Ultimately, they found that there appeared to be a decrease in insulin secretion after increased NNS consumption. Therefore, participants who consumed saccharin or sucralose were more likely to have elevated blood sugar (7). If the non nutritive sweetener was paired with a caloric sweetener like glucose, there would be a higher insulin response compared to NNS alone.
Importantly, the researchers propose that the microbiome may respond to these alternative sweeteners. The results from the microbiome samples suggest that the microbiome may mediate the body’s response to artificial sweeteners . One proposed mechanism for this finding is that bacteria in the gut may be able to metabolize the carbohydrates found in NNS and use them as a source of energy. By using them, the bacteria are therefore decreasing the effect of the artificial sweeteners on the body (7). The scientists note that this theory would need to be corroborated by future research in this area.
While our understanding of non-nutritive sugars may still be shifting, research done so far suggests that the true effects of these sweeteners may not be as sweet as we originally thought. Though these sugary replacements may seem like an easy choice in the grocery store, reducing sugar intake as a whole may be the best solution for our bodies.
1. O’Connor A, Steckelberg A, Reiley L. How fake sugars sneak into foods and disrupt metabolic health [Internet]. Washington Post. [cited 2023 May 14]. Available from: https://www.washingtonpost.com/wellness/interactive/2023/sugar-substitutes-health-effects/
4. Davidson TL, Martin AA, Clark K, Swithers SE. Intake of High-intensity Sweeteners alters the Ability of Sweet Taste to Signal Caloric Consequences: Implications for the Learned Control of Energy and Body Weight Regulation. Q J Exp Psychol 2006. 2011 Jul;64(7):1430–41.
6. Artificial sweeteners linked to risk of weight gain, heart disease and other health issues [Internet]. ScienceDaily. [cited 2023 Apr 24]. Available from: https://www.sciencedaily.com/releases/2017/07/170717091043.htm
7. Suez J, Cohen Y, Valdés-Mas R, Mor U, Dori-Bachash M, Federici S, et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022 Sep 1;185(18):3307-3328.e19.