February 2025 Issue
An Update on Nonnutritive Sweeteners
By Alexandria Hardy, RDN, LDN
Today’s Dietitian
Vol. 27 No. 2 P. 14
Benefits, Risks, and Recommendations
Artificial sweeteners, also called alternative, nonnutritive, and low- or no-calorie sweeteners, are a popular ingredient in many foods and beverages.1 Consumption of artificial sweeteners remains steady over the past two years, with the most popular including stevia-based sweeteners, monk fruit sweeteners, and aspartame.2 This article will focus on their role in foods and beverages and specifically how research and recommendations have evolved in recent years.3
Who Uses Artificial Sweeteners?
According to a consumer survey, Public Perceptions of Dietary Sweeteners published in 2023 by the International Food Information Council, 28% of Americans report regularly and intentionally using low- or no-calorie sweeteners.2 Over 50% of people believe that eating and drinking products with no- or low-calorie sweeteners may improve their health.2
Overview of Common Alternative/Artificial Sweeteners
Artificial sweeteners create a sweet taste by stimulating sweet-taste receptors in the mouth, which then send signals to the brain. Recent research shows that these sweet-taste receptors are also located in other parts of the body like the gastrointestinal tract, pancreas, brain, and fat tissue.4 This discovery suggests that nonnutritive sweeteners (NNSs) may have broader effects on metabolism, as seen in various lab, animal, and human studies.4
Sucralose
Sucralose, more commonly known as Splenda, is a NNS that is 600 times sweeter than sugar.5 It’s often used in beverages, cooking, and baking and is made from sugar through a process that replaces three hydroxyl groups on the sugar molecule with chlorine atoms. Sucralose is minimally absorbed by the body and is primarily excreted unchanged in the urine, which contributes to its zero-calorie nature.5
Recent concerns have arisen regarding sucralose intake and cancer risk, specifically in regard to sucralose’s chemical instability.5 It can release chlorinated aromatic polycyclic hydrocarbons, which are toxic compounds that may be carcinogenic in large quantities in the body.5 These studies have primarily been carried out via mouse models and more well designed research is needed in large, stratified human populations to better understand the risk of sucralose consumption and cancer. Additional research from Advances in Nutrition indicates sucralose may negatively impact insulin sensitivity and glucose metabolism, particularly in individuals with increased gastrointestinal permeability, such as those with obesity or diabetes.6 While earlier studies indicated no impact, methodological limitations highlight the need for more robust, long-term trials using precise techniques to clarify sucralose’s effects on glucose homeostasis. There is also more research that needs to be conducted regarding sucralose metabolism and absorption in specific populations, like children and pregnant and lactating women, as sucralose can cross the placenta.7
Aspartame and Acesulfame-K
Nearly 200 times sweeter than sugar, aspartame is also known as Nutrasweet, Equal, and Sugar Twin.8 Chemically, aspartame is a dipeptide containing aspartic acid and phenylalanine, which when combined yield a sweet flavor. Aspartame is typically used in beverages, gum, syrup, and tabletop sweeteners. Acesulfame-K is a similar sweetener that is often consumed in similar ways and studied alongside aspartame.
A systematic review and meta-analysis in Advances in Nutrition examined the effects of both NNSs on appetite and satiety and determined that they significantly reduced energy intake compared with sugar and water but did not reliably affect blood glucose, subjective appetite scores, or incretin hormone levels.9 Additional high-quality studies are needed to clarify their metabolic effects at dietarily relevant levels.
There have long been questions of whether aspartame intake is linked to neurological disease and cancer. Per the National Cancer Institute, there is no clear association between aspartame consumption and increased risk for cancer.10 The FDA and the Joint Food and Agricultural Organization (JECFA)/World Health Organization Expert Committee on Food Additives consider aspartame safe when consumed within approved levels, and JECFA has not changed the acceptable daily intake. Aspartame is one of the most widely studied food additives, and many regulatory authorities worldwide, including Health Canada and the European Food Safety Authority, also deem it safe.8
Sugar Alcohols
The most consumed sugar alcohols include erythritol, xylitol, and sorbitol. They are also known as “modified sugars” and are less sweet than sucralose and aspartame.11 They are frequently found in sugar-free candies, chewing gum, and desserts and can be mixed with other types of artificial sweeteners to make them more palatable.11 When consumed in large quantities or by those who may be more sensitive to their effects, they can cause gastrointestinal distress, including bloating, gas, and diarrhea, because they are poorly absorbed.12 Erythritol is generally better tolerated as it is more readily absorbed with fewer gastrointestinal side effects than xylitol and sorbitol.12
Stevia
Steviol glycosides are a type of sweet compound that comes from the leaves of a South American plant called Stevia rebaudiana Bertoni.13 The most well-known commercial sweeteners are stevioside and rebaudioside A (Reb A), which is also known as stevia.13 They are chemically and structurally different, with Reb A (stevia) used more commonly in foods and beverages as it tends to have a less bitter flavor and no licorice aftertaste, which can be tasted after consuming stevioside.14 Stevia is commonly used in desserts, baked goods, dairy products, drinks, and condiments.13 Conversion of stevioside and rebaudioside A into steviol occurs in the liver, which is then excreted through urine.15 Oral consumption of stevioside at the recommended dose of 4 mg/kg is safe, nonteratogenic, and noncarcinogenic.15 More human studies are needed to determine why stevia and stevioside may have different pharmacological effects.15
Monk Fruit
Monk fruit, locally known as luo han guo or lo han kuo, is a popular zero-calorie natural sweetener that is 100 to 300 times as sweet as sugar.16,17 The fruit has been used in traditional Chinese medicine for centuries but was only approved as a sweetener in the United States by the FDA in 2010. It can be mixed with other sweeteners like erythritol or sucralose and is often found in a granular or liquid form for baking and cooking. It is generally recognized as safe (GRAS) and its sweetness is attributed to a group of natural compounds known as mogrosides, with mogroside V being most abundant. Monk fruit does not contain carbohydrates and thus has been recommended for use in those with diabetes.18
Allulose
Allulose, also known as D-allulose, is a rare, naturally occurring sugar found in small amounts in plant foods, but it is also commercially produced from corn or fructose. It contains only 10% of the calories of table sugar and is minimally absorbed. When combined with erythritol, it has the potential to exert a positive effect on the hunger hormone ghrelin and improve glycemic control.19 The FDA has approved allulose as safe for consumption, and while it is not yet widely used, it has potential as a low-calorie sweetener in food and beverages.
FDA Classification and Safety of NNS
There are several different metrics used to help determine the safety of NNSs. One is establishing the Acceptable Daily Intake or ADI. These limits represent the number of packets considered safe to consume daily without causing harm.8 For example, the ADI for aspartame (Equal) is 75 packets, while the ADI for sucralose (Splenda) is 23 and the ADI for saccharin (Sweet N’Low) is 45.8 Rebaudioside A based sweeteners like Truvia and PureVia clock in at 27.8 Dietitians can help translate this information for their clients by explaining that each packet contains 2 tsp or 8 g of sweetener, and helping them identify and sum up different sources of NNSs in their diet.
Another common methodology for establishing safety for NNSs is to assign them a GRAS status. GRAS refers to substances that are added to food that are considered safe by qualified experts and do not require premarket approval by the FDA unless they are classified as food additives.20 GRAS sweeteners in the United States include saccharin, aspartame, sucralose, neotame, acesulfame-K, allulose, and stevia; sugar alcohols are also recognized as safe.8,21
Latest Research on Health Impacts of Alternative Sweeteners
Research on NNS is ever evolving as more products hit the market and are consumed in different quantities in different populations. Below are recent research highlights from five specific health indicators.
Gut Microbiome
The effects of NNSs on gut microbiota are still being explored, with studies showing mixed results. NNSs can alter gut microbial composition and metabolic activity, potentially reducing beneficial bacteria while increasing pathogenic strains, which may lead to inflammation, gut dysbiosis, and changes in glucose metabolism. 22 These effects, including shifts in short-chain fatty acid production, bile acid levels, and gut hormone release, highlight their potential role in metabolic and inflammatory diseases.22 While regulatory bodies like the FDA and the European Food Safety Authority broadly deem NNSs safe within ADI limits, different NNSs may each react differently in the gut.4,23 For example, sucralose can potentially alter gut microbiota composition but aspartame does not, and sugar alcohols may promote beneficial bacteria and bolster production of short-chain fatty acids.4,24
Further research is needed to better understand how and why different types and doses of NNSs affect the gut and hunger hormone signaling and how long their impact lasts.4,24 It’s important to note that not all NNS research can be broadly applied, owed to the different chemical compositions of each type. A summary of preclinical and clinical data published in Nutrients further supports this idea, citing conflicting results of NNS impact on the type and number of bacteria present in the microbiome due to factors like diet, lifestyle, and our natural and built environments.22
Metabolic Health
A review published in Cureus evaluated the impact of NNSs on human health to determine risks and benefits of consumption. The review found that there was a significant association between NNS intake and blood sugar (increased fasting levels and A1c as well as impaired glucose tolerance), weight gain in the midsection, and higher alanine aminotransferase levels, which can signal liver impairment.25-27 There was also a positive correlation between intake and delayed stomach emptying and intestinal transit; this may lead to increased gastrointestinal distress.25
CVD
The relationship between NNSs and CVD risk is unclear, with some studies showing direct associations with adverse outcomes while others find no harm. Data from the NutriNet-Santé cohort suggest that NNS intake, including aspartame, acesulfame-K, and sucralose, is linked to increased risks of cerebrovascular events and coronary heart disease.28 These findings indicate that replacing added sugars with some NNS may not provide cardiovascular benefits.25,29 Emerging evidence from Advances in Nutrition suggests sucralose may interact with bitter receptors called TAS2Rs in the cardiovascular system, potentially influencing blood pressure and vascular health through inotropic and vasodilator effects. However, further clinical studies are needed to clarify its long-term impact on cardiometabolic health.6
Neurological Impacts
Aspartame is the primary NNS that has been linked to neurological symptoms such as headaches, migraines, seizures, anxiety, depression, and insomnia.25 Its components, phenylalanine and aspartate, can increase brain levels of certain compounds that disrupt neurochemical balance, affecting dopamine, norepinephrine, and serotonin regulation.25 Additionally, aspartame may act as a chemical stressor by raising cortisol levels and oxidative stress, potentially worsening neurobehavioral health and contributing to migraine pathophysiology through serotonin-related vascular changes.25 There is also mixed research that indicates that long-term consumption of NNS can change the way the brain responds to sweet tastes and how it differentiates and responds to nutritive and NNS.30 More research is needed to confirm these findings and determine the long-term effects of NNS on sweet taste perception.30
Cancer
Research on NNSs and cancer risk shows mixed findings.25,29 While early animal studies suggest a potential carcinogenic effect of aspartame (particularly with prenatal exposure) these results have not been consistently replicated in human studies. Systematic reviews and meta-analyses of human data show no significant association between NNSs and cancer risk, with some even suggesting a reduced risk of urinary system cancers in women.25 However, a large scale population-based study published in PLoS Med found an increased overall cancer risk in individuals who regularly consumed high quantities of aspartame and acesulfame-K; aspartame was also associated with a higher risk of breast and obesity-related cancers.28
Evidence-Based Recommendations for Dietitians
The World Health Organization recommends that added sugar should comprise no more than 5% of total energy intake, which is significantly lower than the average American intake of about 13%.3 Dietitians can guide clients in choosing sweeteners based on their unique metabolic profiles and needs, as research on the impact of low- or no-calorie sweeteners on health remains inconclusive.
While individual sweeteners may appeal to different clients based on personal preferences, an important piece of advice for dietitians is to encourage balanced dietary patterns, including a variety of nutrient-dense whole foods providing sufficient macro and micronutrients. This approach is likely to ensure high dietary quality and minimize the impact of occasional sweetener use.
For clients who rely heavily on products featuring NNSs, offering specific swaps with a similar textural or flavor profile may be helpful. For example, encouraging a fruit and mint infused sparkling water as a substitute for a drink sweetened with an NNS may still provide the fizz and light sweetness they crave. As always, RDs should take each client’s goals and health into consideration as they provide individualized education and recommendations, most effectively made by staying abreast of new research surrounding NNSs.
Conclusion
Enjoying something sweet is a natural and joyful part of eating, and dietitians are positioned to help their clients navigate research and guidelines to make the best choices for their specific nutrition goals. Though research is inconclusive and ongoing, most studies indicate that there just isn’t enough high quality, evidence-based research available to support higher intakes of NNS in the diet.
— Alexandria Hardy, RDN, LDN, is an early intervention nutrition therapist, and the owner of Pennsylvania Nutrition Services, an insurance-based private practice located in Lancaster, Pennsylvania.
References
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