Introduction to Non-Nutritive Sweeteners (NNS)

Non-nutritive sweeteners (NNS) are sugar substitutes that provide intense sweetness with minimal to no caloric value. They are commonly used in place of sugar in foods and beverages, allowing for sweetness without the calories or blood sugar impact of regular sugar. NNS can be beneficial for managing calorie intake, blood glucose levels, and certain metabolic conditions. However, understanding their metabolic processing, physiological impact, and contraindications is essential for effective use in culinary medicine.

Examples of Common Non-Nutritive Sweeteners:

Aspartame (Equal, NutraSweet)
Sucralose (Splenda)
Saccharin (Sweet 'N' Low)
Acesulfame-K (Sweet One)
Steviol glycosides (Stevia)
Monk Fruit Extract

Categories of Substitute Sweeteners

There are two categories of non-nutritive sweeteners: artificial and natural. In addition, sugar alcohols are considered a substitute sweetener for table sugar, but do provide some calories, but lesser amounts than sugar.

Non-Nutritive Sweeteners: Artificial Sweeteners

https://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states
Dudek, S. G. Nutrition essentials for nursing practice. 9th edition, Wolters Kluwer, 2022, pp 55.

Artificial sweeteners have little to no calories. Some pass completely through the body.

Looking at the third column on the table, sweetness intensity for each is compared to table sugar. For example, saccharin is 200 to 700 times sweeter than sugar. As such, less is needed in products. The FDA has deemed all of these as safe for use within the ADI or acceptable daily intakes listed as milligrams per kilogram of body weight daily. Although some do have bitter aftertastes at high concentrations, others have closer taste profiles to table sugar (sucrose).

A large, prospective cohort study in France1 showed a correlation between the artificial sweeteners aspartame, acesulfame potassium and sucralose and cerebrovascular disease risk

It is reasonable to recommend artificial sweeteners to your patients but in moderation. Occasional use in coffee or tea is very reasonable, but moving away from artificially sweetened products is the best strategy.

Non-Nutritive Sweeteners: Natural

Unlike artificial sweeteners, natural non-nutritive sweeteners are derived from foods. Some are high intensity sweeteners such as Reb M, Steviol glycosides and Luo Han Guo Fruit extracts, so very little is needed. In fact, they often fall under the category of a natural flavoring agent.

Allulose and tagatose provide the bulk and strength of sweetness similar to sugar.

Nutritive Sweeteners: Sugar Alcohols2,3
Xylitol
Erythritol
Manitol
Sorbitol
Maltitol
Isomalt
Lactitol
Hydrogenated Starch Hydrolysates

Another category of nutritive sweeteners are sugar alcohols or polyols.

Though they are found naturally in some fruits and vegetables, commercially they are derived from sugars and starch. They are considered carbohydrates with less calories and even lower when paired with non-nutritive sweeteners.

They confer the health benefits of no glucose surge response and are safe when consumed in moderation. Excessive consumption results in GI upset or laxative effect. It is important to note that more studies on the long-term safety of erythritol are warranted after recent research points to a significantly increased risk of heart attacks and stroke.

Sweetness Intensity and Culinary Uses

NNS are typically much sweeter than sugar, ranging from 200 to over 600 times the sweetness of sucrose (table sugar). Only a small quantity is required for recipes, and some NNS can be blended with bulking agents to mimic sugar's volume and texture.

Aspartame: Approximately 200 times sweeter than sugar, commonly used in beverages and dairy products.

Sucralose: 600 times sweeter than sugar and heat-stable, suitable for baking and cooking.

Stevia and Monk Fruit Extract: Natural sweeteners derived from plants, popular for their clean sweetness and natural origin.

Mechanism and Impact on Blood Glucose

Unlike sugar, NNS have minimal to no impact on blood glucose and insulin levels. Their metabolic processing varies depending on the specific sweetener:

Stevia and Monk Fruit Extract:

Processing in the Body: Stevia contains compounds called steviol glycosides, which are absorbed by the gut, metabolized by the liver, and ultimately excreted in the urine. The primary glycoside, stevioside, is converted in the liver to steviol, a molecule that does not affect blood glucose levels.

Monk Fruit: Monk fruit extract contains mogrosides, which are metabolized in the liver. The mogrosides are broken down into glucose and other molecules, but the glucose is not absorbed into the bloodstream; rather, it is metabolized in the liver and excreted without raising blood sugar levels.

Impact on Blood Glucose: Both stevia and monk fruit have negligible effects on blood glucose, making them favorable for individuals with diabetes or those looking to manage blood sugar.

Aspartame:

Processing in the Body: Aspartame is metabolized differently than other NNS. It breaks down into three components in the digestive tract: phenylalanine, aspartic acid, and methanol. While aspartame itself provides minimal calories, it is metabolized by the liver, and these breakdown products are used in normal metabolic pathways.

Impact on Blood Glucose: Aspartame has little to no direct effect on blood glucose. However, people with the rare genetic disorder phenylketonuria (PKU) must avoid aspartame, as they cannot metabolize phenylalanine effectively.

Sucralose:

Processing in the Body: Sucralose is mostly unabsorbed and is excreted unchanged in the feces. A small percentage is absorbed but excreted via urine without significant metabolic alteration.

Impact on Blood Glucose: Sucralose does not impact blood glucose or insulin levels, making it suitable for individuals who need stable glucose levels.

Health Implications

Weight Management: Allulose shows promising health benefits, largely in animals studies, but also in human ones. In fact, a randomized, double-blind, placebo control trial of 121 overweight and obese Koreans were given low- and high-doses of Alllulose beverages twice a day compared to a control group who drank Sucralose beverages. This was done for 12 weeks and afterward, Allulose participants lost weight, body fat percentage and abdominal subcutaneous fat significantly more than the control group. The participants given larger doses of Allulose (14 grams/day versus 8 grams) had more reductions, showing the more Allulose the more benefit4.

Evidence: Substituting sugar with NNS can reduce overall caloric intake, aiding in weight management (Malik et al., 2019).

Application: In culinary medicine, NNS can reduce caloric density in recipes, benefiting patients aiming for weight loss or maintenance.

Diabetes Management: A systematic review and meta analysis on allulose discovered it reduced the glucose surge after a meal by 10%5.

Blood Sugar Stability: For individuals with diabetes, NNS provide sweetness without the rapid blood sugar spikes associated with sugar, allowing for better glycemic control (Ashwell, 2015).

One randomized control study of people with type 2 diabetes using Stevia in their tea for eight weeks found it did not increase blood sugar levels. In fact, a small crossover study comparing stevia to corn starch consumption even found stevia to lower blood sugar levels6.  Though a metanalysis of 9 randomized control trials found stevia did not lower (or raise) blood sugar levels, but it significantly lowered systolic blood pressure7.

Guidelines: The American Diabetes Association supports the use of NNS in moderation to provide low-calorie options without affecting glycemic levels.

Oral Health: Unlike sugar, NNS are not metabolized by oral bacteria, reducing the risk of tooth decay. This feature is beneficial in dietary counseling, particularly for patients with higher dental caries risk.

Contraindications and Considerations

While NNS are generally safe for most people within the established Acceptable Daily Intake (ADI) levels, certain groups should exercise caution or avoid specific sweeteners:

Aspartame and Phenylketonuria (PKU): Phenylketonuria (PKU): Individuals with PKU, a rare genetic disorder, cannot metabolize phenylalanine, a component of aspartame. Aspartame is contraindicated in individuals with PKU and must be avoided completely.

Pregnancy: Saccharin: While saccharin is approved for use, some health organizations suggest that pregnant women should avoid it. Saccharin crosses the placenta and may accumulate in fetal tissues, though its long-term effects remain unclear. Alternative sweeteners like stevia or monk fruit may be preferred during pregnancy.

Digestive Sensitivity and Gastrointestinal Discomfort:

Sugar Alcohols (e.g., sorbitol, erythritol): Although technically not non-nutritive, sugar alcohols are often used as low-calorie sweeteners and can cause gastrointestinal discomfort (bloating, gas, and diarrhea) in sensitive individuals. Those with irritable bowel syndrome (IBS) or other digestive disorders may want to limit their intake. Erythritol has been linked to

Gut Health Considerations: Some research suggests that certain artificial NNS, particularly saccharin, may disrupt gut microbiota composition, potentially impacting metabolism and glucose tolerance in sensitive individuals (Suez et al., 2014). Patients with microbiome-related health concerns may want to limit artificial sweeteners and choose natural options like stevia or monk fruit.

Potential Allergies: Although rare, some people may experience mild allergic reactions to certain NNS, such as sucralose or aspartame. Symptoms may include headaches, rashes, or digestive upset. If adverse reactions occur, it is recommended to discontinue the use of the specific NNS and consult a healthcare provider.

Pediatric Use: Children's intake of NNS should be closely monitored due to their smaller body size and higher sensitivity to taste changes. NNS use in children is typically limited to medical needs, such as diabetes management, with oversight to avoid excessive use and reliance on sweet flavors.

Safety and Controversies

NNS are approved by regulatory agencies such as the FDA and EFSA, with Acceptable Daily Intake (ADI) levels established for each type. However, concerns about long-term health effects continue to be debated. Key areas include:

Gut Health: Some studies indicate that certain artificial NNS, such as saccharin, may alter gut microbiota composition, which could impact glucose metabolism. However, more research is needed to fully understand these effects (Suez et al., 2014).

Metabolic Impact: Although NNS generally do not impact blood glucose, some research suggests that regular NNS use could alter taste perception and appetite regulation, potentially affecting cravings and eating behaviors over time (Yang, 2010).

Cancer Risks: Early studies linked saccharin to bladder cancer in animal models, but subsequent human research has not confirmed these findings. Most NNS are considered safe within the established ADI levels based on current evidence.

Practical Culinary Applications

Baking and Cooking: Heat stability varies among NNS. For example, sucralose, stevia, reb-M can withstand high temperatures, making them suitable for baked goods, whereas aspartame breaks down with heat.

Because Tagatose is so similar in sweetness, taste, and bulk as sugar, it can be used much like sugar. The melting point and ability to caramelize, providing a malty flavor profile also provides culinary benefits. It is important to note that when used for cookies it creates a cakey consistency.

Recipe Adjustments: Due to their potency, NNS require reduced quantities in recipes. Culinary professionals often use NNS blends with bulking agents to replicate sugar's texture.

Cold Applications: NNS work well in cold preparations, such as smoothies, salad dressings, and desserts like custards or frozen treats, where they provide sweetness without textural changes.

Preferred Sweeteners: Natural sweeteners like monk fruit and stevia are often preferred for cold dishes due to their clean taste.

Blending with Sugar: In some recipes, a small amount of sugar can be combined with NNS to balance flavor and provide bulk, particularly in baked goods that rely on sugar's structure.

References

Debras, Charlotte et al. "Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santécohort." BMJ (Clinical research ed.) vol. 378 e071204. 7 Sep. 2022, doi:10.1136/bmj-2022-071204

Plaza-Diaz, Julio et al. "Plausible Biological Interactions of Low- and Non-Calorie Sweeteners with the Intestinal Microbiota: An Update of Recent Studies." Nutrients vol. 12,4 1153. 21 Apr. 2020, doi:10.3390/nu12041153

Witkowski, Marco et al. "The artificial sweetener erythritol and cardiovascular event risk." Nature medicine vol. 29,3 (2023): 710-718. doi:10.1038/s41591-023-02223-9

Han, Y., Kwon, E.-Y., Yu, M., Lee, S., Kim, H.-J., Kim, S.-B., Kim, Y., Choi, M.-S., 2018. A Preliminary Study for Evaluating the Dose-Dependent Effect of d-Allulose for Fat Mass Reduction in Adult Humans: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients 10, 160.. doi:10.3390/nu10020160

Kendall, John L. Sievenpiper, Effect of fructose and its epimers on postprandial carbohydrate metabolism: A systematic review and meta-analysis. Clinical Nutrition, Volume 39, Issue 11, 2020, Pages 3308-3318.

Gregersen, Søren et al. "Antihyperglycemic effects of stevioside in type 2 diabetic subjects." Metabolism: clinical and experimental vol. 53,1 (2004): 73-6. doi:10.1016/j.metabol.2003.07.013

Bundgaard Anker, Camilla Christine et al. "Effect of Steviol Glycosides on Human Health with Emphasis on Type 2 Diabetic Biomarkers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Nutrients vol. 11,9 1965. 21 Aug. 2019, doi:10.3390/nu11091965