Sweet Alternatives and Health: Guidance for Health Professionals

Low calorie sweeteners (LCS) can be used in certain patient populations. LCS contribute no calories or negligible calories in small quantities. LCS’s may come directly from plants, industry produced from naturally occurring foods or be newly synthesized chemical compounds.

Plant-based LCS’s are preferential to synthetic. Chemically synthesized LCS’s have the potential to be detrimental to human health. In contrast, plant-based LCS’s may have a beneficial role in human health.

Results of LCS and human health studies are mixed. Data primarily reflect  animal models or human adult research. Adverse effects in children and pregnant women are not well understood with some evidence for harm from exposure in utero. Further research is needed to adequately inform dietary recommendations.

Background

Dietary sugars can be naturally occurring or added. To replace added sugars, low calorie sweeteners (nutritive and non-nutritive) are commonly used.

• Naturally occurring sugars are part of whole fruits and vegetables, and unsweetened dairy products (e.g. milk, yogurt).
• Added sugars include addition of sugars during food production. Pure (100%) honey, pure (100%) maple syrup, and other single-ingredient sugars, such as juice concentrates, contribute to the daily value of added sugars.
• Low calorie sweeteners—are an alternative product used to add sweetness that contains zero (non-nutritive) or very low amounts (nutritive) or carbohydrates.

Health Effects of Added Sugar

• Added sugars increase the risk of chronic disease in adult and pediatric populations
• The U.S. Dietary Guidelines for Americans recommend limiting calories from added sugars to no more than 10% of total daily calories. These guidelines are supported by the Centers for Disease Control and Prevention, and World Health Organization.

Low Calorie Sweeteners (LCS)

• Offer an opportunity to consume sweet tasting products without added calories.
• May support a healthy body weight, as well as diabetes and cardiovascular disease management in adult and pediatric populations, and during pregnancy.

LCS and Maternal-Fetal and Pediatric Implications

• Studies primarily limited to animal and adult-human studies.
• American Academy of Pediatrics recommends more research to better understand possible health effects in children long-term.
• The American College of Obstetricians and Gynecologists have not made any statement on LCS consumption during pregnancy.
• Associations found in human studies, LCS unspecified.
  • Maternal intake of LCS-containing beverages during pregnancy increased risk of gestational diabetes and preterm delivery.
  • Maternal intake of LCS-containing beverages during pregnancy increased risk of childhood asthma.
  • Maternal consumption of LCS-containing beverages increased infant BMI and increased risk of being overweight at 1 year of age. In addition, a clinical trial demonstrated maternal consumption of LCS-containing beverages led to unfavorable shifts in infant gut microbiome.  

LCS may be further divided into the following categories, with clinical health impacts listed in the tables below. These Sweeteners are approved in the USA and meet GRAS classification (Generally Recognized as Safe) by the FDA.

Plant Based Sweeteners

Sweetener/Brand Names	Clinical health impacts
Stevia (Candyleaf plant)/ Truvia, Pure Via, Enliten	Reduced body weight, decreased plasma glucose, and improved insulin sensitivity. When compared to aspartame and sucrose, significantly reduced postprandial glucose.   Anticarcinogen in human cancer cell lines.
Monk Fruit (Luo Han Guo plant)/ Monk Fruit in the Raw, PureLo, Nectresse	Beneficial for preventing hyperglycemia and insulin secretion.   Anticarcinogen in human cancer cell lines.
Yacon (Yacon plant)	Beneficial for bowel function as a source of fructooligosaccharides. Reduced body weight, improved insulin sensitivity and satiety. Anticarcinogen in human cancer cell lines.
Thaumatin (West African Katemfe Fruit)/ Talin	Few long-term human studies. No significant effect on glycemic response for healthy individuals. Decreased blood glucose in Type 2 diabetics. Reduced H. pylori-induced pro-inflammatory cytokines in human parietal cells.

Sweeteners Derived From Naturally Occurring Foods

Sweetener/Brand Names	Clinical health impacts
Tagatose	Beneficial effects for oral and colonic microbiome. Reduced circulating tagatose correlates with the development of inflammatory bowel disease. Antihyperglycemic, decreased postprandial glycemic response, and improved satiety.   Inhibitory effects on colon cancer in human cell lines.
Allulose	Improved insulin sensitivity and lowered postprandial glycemic response. Anticarcinogen in human cancer cell lines.
Sugar alcohols (e.g. Erythritol, Mannitol, Isomaltitol, Lactitol, Sorbitol, Xylitol)	Beneficial effects on the microbiome possibly due to a prebiotic-like effect. In larger quantities, can increase blood glucose. In moderate amounts, lowered postprandial plasma glucose. Increased cancer risk (hepatocellular carcinoma).   Studies of erythritol and xylitol show an association with incident major adverse cardiovascular events and thrombosis.

New Chemical Compound Sweeteners

Sweetener/Brand Names	Clinical health impacts
Aspartame/ NutraSweet, Equal, Sugar Twin	Aspartame has demonstrated a favorable microbiome shift, poorer glucose control, and increased cancer risk with consumption in some studies. Aspartame has been associated with risk for cognitive deficits, mood disorders, headaches, and seizures. Association between autism in males and maternal aspartame intake in pregnancy.
Advantame	Neotame and advantame are derived from aspartame. Neither has been evaluated in human studies.
Neotame/ Newtame
Acesulfame potassium “Ace-K”/ Sunett, Sweet One	Ace-K is commonly used in combination with other LCS (commonly Aspartame) — isolated effects are poorly understood. Has demonstrated a slightly higher risk of cancer overall, less than aspartame.
Saccharin/ Sweet and Low, Sweet N’ Low, Sugar Twin, Necta Sweet	Both Saccharin and Sucralose have demonstrated unfavorable shifts in the microbiome and poorer glucose control for in some studies. Cancer risk not observed in humans (bladder cancer in rats).
Sucralose/ Splenda
Combined Exposures	Maternal intake of Saccharin, Aspartame, Ace-K, and Sucralose during pregnancy contributes to gestational weight gain, increased childhood BMI, and increased insulin resistance.   Combination sucralose and Ace-K containing beverages lessen BMI gain in adolescents. Intake of Aspartame, Ace-K, and Sucralose linked to higher risk of any cardiovascular problem, risk of stroke, and developing type 2 diabetes. Beverages containing sucralose or aspartame do not raise postprandial blood glucose or insulin levels to the same extent as sucrose.

By: Elizabeth Reznikov, DO, PhD

References:

• Gillespie, K. M., Kemps, E., White, M. J., & Bartlett, S. E. (2023). The impact of free sugar on human health—a narrative review. Nutrients, 15(4), 889.
• Huang, Y., Chen, Z., Chen, B., Li, J., Yuan, X., Li, J., Wang, W., Dai, T., Chen, H., Wang, Y. and Wang, R. (2023). Dietary sugar consumption and health: umbrella review. Bmj, 381.
• U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th edition. Dietary Guidelines for Americans, 2020-2025
• Palatnik, A., Moosreiner, A., & Olivier-Van Stichelen, S. (2020). Consumption of non-nutritive sweeteners during pregnancy. American journal of obstetrics and gynecology, 223(2), 211-218.
• Kearns, M. L., & Reynolds, C. M. (2024). The impact of non-nutritive sweeteners on fertility, maternal and child health outcomes–a review of human and animal studies. Proceedings of the Nutrition Society, 1-33.
• Maslova, E., Strøm, M., Olsen, S. F., & Halldorsson, T. I. (2013). Consumption of artificially-sweetened soft drinks in pregnancy and risk of child asthma and allergic rhinitis. PloS one, 8(2), e57261.
• Englund-Ögge, L., Brantsæter, A. L., Haugen, M., Sengpiel, V., Khatibi, A., Myhre, R., Myking, S., Meltzer, H.M., Kacerovsky, M., Nilsen, R.M.,Jacobsson, B. (2012). Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study. The American journal of clinical nutrition, 96(3), 552-559.
• Azad, M. B., Sharma, A. K., de Souza, R. J., Dolinsky, V. W., Becker, A. B., Mandhane, P. J., Turvey, S.E., Subbarao, P., Lefebvre, D.L., Sears, M.R., Canadian Healthy Infant Longitudinal Development Study Investigators. (2016). Association between artificially sweetened beverage consumption during pregnancy and infant body mass index. JAMA pediatrics, 170(7), 662-670.
• Laforest-Lapointe, I., Becker, A. B., Mandhane, P. J., Turvey, S. E., Moraes, T. J., Sears, M. R., Subbarao, P., Sycuro, L.K., Azad, M.B., Arrieta, M.C. (2021). Maternal consumption of artificially sweetened beverages during pregnancy is associated with infant gut microbiota and metabolic modifications and increased infant body mass index. Gut Microbes, 13(1), 1857513.
• Gebremichael, B., Lassi, Z. S., Begum, M., & Zhou, S. J. (2025). Association between low‐calorie sweetener consumption during pregnancy and child health: A systematic review and meta‐analysis. Maternal & Child Nutrition, 21(1), e13737.
• Singh, G., McBain, A. J., McLaughlin, J. T., & Stamataki, N. S. (2024). Consumption of the Non-Nutritive Sweetener Stevia for 12 Weeks Does Not Alter the Composition of the Human Gut Microbiota. Nutrients, 16(2), 296.
• Movahedian, M., Golzan, S. A., Asbaghi, O., Prabahar, K., & Hekmatdoost, A. (2024). Assessing the impact of non-nutritive sweeteners on anthropometric indices and leptin levels in adults: A GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials. Critical Reviews in Food Science and Nutrition, 64(30), 11161-11178.
• Iatridis, N., Kougioumtzi, A., Vlataki, K., Papadaki, S., & Magklara, A. (2022). Anti-cancer properties of Stevia rebaudiana; more than a sweetener. Molecules, 27(4), 1362.
• Anton, S. D., Martin, C. K., Han, H., Coulon, S., Cefalu, W. T., Geiselman, P., & Williamson, D. A. (2010). Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite, 55(1), 37-43.
• Pandey, A. K., & Chauhan, O. P. (2019). Monk fruit (Siraitia grosvenorii)-health aspects and food applications.
• Haung, R., Saji, A., Choudhury, M., & Konno, S. (2023). Potential Anticancer Effect of Bioactive Extract of Monk Fruit (Siraitia grosvenori) on Human Prostate and Bladder Cancer Cells. Journal of Cancer Therapy, 14(5), 211-224.
• Yan, M. R., Welch, R., Rush, E. C., Xiang, X., & Wang, X. (2019). A sustainable wholesome foodstuff; health effects and potential dietotherapy applications of yacon. Nutrients, 11(11), 2632.
• Machado, A. M., da Silva, N. B., Chaves, J. B. P., & Rita de Cássia, G. A. (2019). Consumption of yacon flour improves body composition and intestinal function in overweight adults: A randomized, double-blind, placebo-controlled clinical trial. Clinical nutrition ESPEN, 29, 22-29.
• EFSA Panel on Food Additives and Flavourings (FAF), Younes, M., Aquilina, G., Castle, L., Engel, K. H., Fowler, P., … & Vianello, G. (2021). Re‐evaluation of thaumatin (E 957) as food additive. EFSA Journal, 19(11), e06884.
• Khayata, W., Kamri, A., & Alsaleh, R. The glycemic effect of thaumatin and its mixture with sucrose in type 2 diabetes patients. World Health, 2, 4.
• Richter, P., Sebald, K., Fischer, K., Schnieke, A., Jlilati, M., Mittermeier-Klessinger, V., & Somoza, V. (2024). Gastric digestion of the sweet-tasting plant protein thaumatin releases bitter peptides that reduce H. pylori induced pro-inflammatory IL-17A release via the TAS2R16 bitter taste receptor. Food Chemistry, 448, 139157.
• Ortiz, A. D. C., Fideles, S. O. M., Reis, C. H. B., Pagani, B. T., Bueno, L. M. M., Moscatel, M. B. M., … & Buchaim, D. V. (2024). D-Tagatose: A Rare Sugar with Functional Properties and Antimicrobial Potential against Oral Species. Nutrients, 16(12), 1943.
• Guerrero-Wyss, M., Durán Agüero, S., & Angarita Dávila, L. (2018). D‐Tagatose is a promising sweetener to control glycaemia: A new functional food. BioMed Research International, 2018(1), 8718053.
• Venema, K., Vermunt, S. H., & Brink, E. J. (2005). D-Tagatose increases butyrate production by the colonic microbiota in healthy men and women. Microbial ecology in Health and Disease, 17(1), 47-57.
• Noguchi, C., Kamitori, K., Hossain, A., Hoshikawa, H., Katagi, A., Dong, Y., … & Yamaguchi, F. (2016). D-allose inhibits cancer cell growth by reducing GLUT1 expression. The Tohoku Journal of Experimental Medicine, 238(2), 131-141.
• Shi, F., Gao, Y. S., Han, S. M., Shi, H., Hou, Q. S., Gao, Y., … & Zou, L. (2024). Targeting MLCK-MLC2 signaling pathway by tagatose alleviates dysregulated mitochondria-associated colonitis. Journal of Functional Foods, 117, 106222.
• Ayesh, H., Suhail, S., & Ayesh, S. (2024). Impact of allulose on blood glucose in type 2 diabetes: A meta-analysis of clinical trials. Metabolism Open, 24, 100329.
• Gauthier, E., Milagro, F. I., & Navas-Carretero, S. (2024). Effect of low-and non-calorie sweeteners on the gut microbiota: A review of clinical trials and cross-sectional studies. Nutrition, 117, 112237.
• Chu, Y. Y., Yang, Y. C. S., Hsu, S. Y., Fan, H. Y., Hwang, L. D., Nacis, J. S., & Chen, Y. C. (2025). Gut microbiome and body composition with sorbitol intake during early lifespan. Nutrition, 130, 112614.
• Ismail, I. T., Fiehn, O., Elfert, A., Helal, M., Salama, I., & El-Said, H. (2020). Sugar alcohols have a key role in pathogenesis of chronic liver disease and hepatocellular carcinoma in whole blood and liver tissues. Cancers, 12(2), 484.
• Msomi, N. Z., Erukainure, O. L., & Islam, M. S. (2021). Suitability of sugar alcohols as antidiabetic supplements: A review. Journal of food and drug analysis, 29(1), 1.
• Witkowski, M., Nemet, I., Alamri, H., Wilcox, J., Gupta, N., Nimer, N., … & Hazen, S. L. (2023). The artificial sweetener erythritol and cardiovascular event risk. Nature medicine, 29(3), 710-718.
• Witkowski, M., Nemet, I., Li, X. S., Wilcox, J., Ferrell, M., Alamri, H., … & Hazen, S. L. (2024). Xylitol is prothrombotic and associated with cardiovascular risk. European Heart Journal, ehae244.
• Kossiva, L., Kakleas, K., Christodouli, F., Soldatou, A., Karanasios, S., & Karavanaki, K. (2024). Chronic Use of Artificial Sweeteners: Pros and Cons. Nutrients, 16(18), 3162.
• NIH National Cancer Institute “Artificial Sweeteners and Cancer.” Artificial Sweeteners and Cancer – NCI
• Conz, A., Salmona, M., & Diomede, L. (2023). Effect of non-nutritive sweeteners on the gut microbiota. Nutrients, 15(8), 1869.
• Ruiz-Ojeda, F. J., Plaza-Díaz, J., Sáez-Lara, M. J., & Gil, A. (2019). Effects of sweeteners on the gut microbiota: a review of experimental studies and clinical trials. Advances in nutrition, 10, S31-S48.
• Lee, C. Y., So, Y. S., Yoo, S. H., Lee, B. H., & Seo, D. H. (2024). Impact of artificial sweeteners and rare sugars on the gut microbiome. Food Science and Biotechnology, 33(9), 2047-2064.
• Debras, C., Chazelas, E., Srour, B., Druesne-Pecollo, N., Esseddik, Y., de Edelenyi, F. S., … & Touvier, M. (2022). Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. PLoS medicine, 19(3), e1003950.
• Dar, W. (2024). Aspartame-induced cognitive dysfunction: Unveiling role of microglia-mediated neuroinflammation and molecular remediation. International Immunopharmacology, 135, 112295.
• Fowler, S. P., Gimeno Ruiz de Porras, D., Swartz, M. D., Stigler Granados, P., Heilbrun, L. P., & Palmer, R. F. (2023). Daily early-life exposures to diet soda and aspartame are associated with autism in males: A case-control study. Nutrients, 15(17), 3772.
• Stepien, M., Duarte-Salles, T., Fedirko, V., Trichopoulou, A., Lagiou, P., Bamia, C., … & Jenab, M. (2016). Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort. European journal of nutrition, 55, 7-20.
• Jones, G. S., Graubard, B. I., Ramirez, Y., Liao, L. M., Huang, W. Y., Alvarez, C. S., … & McGlynn, K. A. (2022). Sweetened beverage consumption and risk of liver cancer by diabetes status: A pooled analysis. Cancer Epidemiology, 79, 102201.
• Debras, C., Chazelas, E., Sellem, L., Porcher, R., Druesne-Pecollo, N., Esseddik, Y., … & Touvier, M. (2022). Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. Bmj, 378.
• Debras, C., Deschasaux-Tanguy, M., Chazelas, E., Sellem, L., Druesne-Pecollo, N., Esseddik, Y., Szabo de Edelenyi, F., Agaesse, C., De Sa, A., Lutchia, R., Julia, C., Kesse-Guyot, E., Alles, B., Galan, P., Hercberg, S., Huybrechts, I., Cosson, E., Tatulashvili, S., Srour, B., Touvier, M. (2023). Artificial sweeteners and risk of type 2 diabetes in the prospective NutriNet-Santé cohort. Diabetes Care, 46(9), 1681-1690.
• Baker-Smith, C. M., De Ferranti, S. D., Cochran, W. J., Abrams, S. A., Fuchs, G. J., Kim, J. H.,  Lindsey, C., Magge, S.N., Romes, E.S., Schwarzenberg, S.J., Lightdale, J.R., Brumbaugh, D., Cohen, M.B., Dotson, J.L., Harpavat, S., Oliva-Hemker, M.M.,  Heitlinger, L. A. (2019). The use of nonnutritive sweeteners in children. Pediatrics, 144(5).
• de Ruyter, J. C., Olthof, M. R., Seidell, J. C., & Katan, M. B. (2012). A trial of sugar-free or sugar-sweetened beverages and body weight in children. New England Journal of Medicine, 367(15), 1397-1406.
• Ebbeling, C. B., Feldman, H. A., Steltz, S. K., Quinn, N. L., Robinson, L. M., & Ludwig, D. S. (2020). Effects of sugar‐Sweetened, artificially Sweetened, and Unsweetened beverages on cardiometabolic risk factors, body composition, and sweet taste preference: a randomized controlled trial. Journal of the American Heart Association, 9(15), e015668.