The Impact of Non-Nutritive Sweeteners on Health and Cancer Risk

Information Guide: The Impact of Non-Nutritive Sweeteners on Health and Cancer Risk

Download the Information Guide (PDF) here.  

Non–nutritive Sweeteners (NNS) are substances used to provide a sweet taste in foods and beverages that deliver little to no calories. They are much sweeter than sugar, so only tiny amounts are required, which helps reduce overall calorie and sugar intake.

NNS can include both synthetic compounds (e.g. aspartame, sucralose, saccharin) and naturally derived compounds (e.g. steviol glycosides from the Stevia plant). This broad category is used to help manage weight, control blood glucose levels, and reduce the risk of dental decay, without the metabolic impact associated with regular sugars. They are widely used in diet drinks, sugar-free foods, and other low-calorie products. Because they are much sweeter than sugar, only very small amounts are needed.¹

However, concerns about health and potential cancer risks have persisted for decades, prompting extensive research and regulatory review.

The ADI is expressed in milligrams of the substance per kilogram of body weight per day (mg/kg bw/day) and is intended to be a level of intake that can safely be consumed every day over a person’s lifetime without appreciable health risk. For example, the EFSA has established an ADI for aspartame of about 40mg/kg bw/day, while in the United States, the FDA has set it at 50mg/kg Non-nutritive Sweeteners (NNS) are substances used to provide a sweet taste in foods and beverages that deliver little to no calories. They are much sweeter than sugar, so only tiny amounts are required, which helps reduce overall calorie and sugar intake.

Safe Amounts and Regulatory Guidelines

To protect public health, organisations like the European Food Safety Authority (EFSA) and the U.S. Food and Drug Administration (FDA) have set advice on how much of each sweetener you can safely consume every day. This limit is called the Acceptable Daily Intake (ADI) and is given in milligrams per kilogram of body weight (mg/kg bw/day). These ADIs are carefully derived from toxicological studies carried out by regulatory bodies around the world.

The ADI is expressed in milligrams of the substance per kilogram of body weight per day (mg/kg bw/day) and is intended to be a level of intake that can safely be consumed every day over a person’s lifetime without appreciable health risk. For example, the EFSA has established an ADI for aspartame of about 40mg/kg bw/day, while in the United States, the FDA has set it at 50mg/kg bw/day. Other sweeteners have their own respective ADI values (see table below) that are used as reference points in dietary guidelines. For example:

• Aspartame: About 40 mg/kg bw (EU) and 50 mg/kg bw (US). For a 70-kg person, this means roughly 2,800–3,500 mg each day.
• Sucralose: Approximately 5 mg/kg
• Saccharin: Around 15 mg/kg
• Steviol Glycosides (from Stevia): About 4 mg/kg bw (expressed as steviol equivalents).

These regulatory agencies, such as EFSA and the FDA, require that manufacturers adhere to these ADI levels. They also mandate thorough pre-market safety evaluations and require that products containing NNS are clearly labelled. Moreover, bodies like the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and regional regulations (for example, in South Africa under the Foodstuffs, Cosmetics and Disinfectants Act) ensure that the sweeteners used in food and beverages are kept within safe limits, complementing Good Manufacturing Practices (GMP) that prevent the product quality from being compromised. These guidelines are dynamic. Re- evaluations by EFSA and other regulatory bodies are ongoing as new scientific evidence emerges. This means that while current ADI values indicate safety at prescribed levels, continuous research ensures that these standards remain protective of public health over time.

How Do Non-Nutritive Sweeteners Work in the Body?

While the established ADIs indicate that NNS are safe for most people when consumed in moderation, some research has raised questions about potential risks. Observational studies have found associations between high consumption of artificially sweetened beverages and an increased risk of metabolic disorders such as type 2 diabetes and cardiovascular diseases.^2–4 Because these studies observe what people do in real life, they may be affected by other lifestyle factors.

• Changing the Gut Bacteria: Your digestive system is home to a vast community of bacteria, which help with digestion and overall Research suggests that NNS can alter gut microbiota composition.⁵ Potentially upsetting how your gut functions and leading to dysbiosis—an imbalance in gut bacteria that may contribute to affecting your metabolism.⁶
• Influencing Blood Sugar and Insulin Release: When you taste something sweet, your brain expects a burst of energy (calories), however, with NNS, the sweetness comes without calories. This mismatch may disrupt your natural hunger cues and lead you to crave more sugary food later by confusing the hunger and insulin-regulation signals.⁷ Some studies suggest that these sweeteners may affect how your body controls blood sugar by altering hormone responses. More advanced research using genetic methods such as Mendelian randomization has even found links between NNS intake (for example, in coffee) and an increased risk of type 2 diabetes, potentially due to changes in cholesterol levels.⁸
• Neurological and Toxicity Concerns: A review highlighted potential neurotoxic effects of NNS, including links to cognitive impairment and mood disorders. Additionally, concerns about bioaccumulation and environmental toxicity have been raised, particularly regarding their persistence in ecosystems.⁹

Health guidelines for NNS vary by organization, but recent recommendations emphasise caution in their use:

• The World Health Organization (WHO) advises against using NNS for weight control or reducing the risk of noncommunicable diseases. Their review suggests that NNS do not provide long-term benefits for body fat reduction and may be linked to increased risks of type 2 diabetes, cardiovascular diseases, and mortality.¹⁰ 
• Harvard School of Public Health supports WHO’s stance, noting that while NNS may reduce calorie intake in the short term, long-term observational studies associate them with higher risks of metabolic disorders. They recommend reducing overall sweetness in the diet rather than substituting sugar with NSS.¹¹ 
• General Dietary Recommendations suggest that NNS like aspartame, sucralose, and saccharin should be consumed within established ADI limits set by regulatory bodies such as the FDA and EFSA. However, emerging research continues to assess their long-term health effects.

Current Evidence Base Regulatory Position

The U.S. FDA has reviewed numerous safety studies for each approved NNS and found no evidence that these sweeteners cause cancer or other harms in people. Similarly, the EFSA sets an ADI for all approved sweeteners that is considered safe for consumption.

WHO/IARC Classification

In July 2023, the International Agency for Research on Cancer (IARC) made a significant classification decision regarding aspartame. IARC classified aspartame as possibly carcinogenic to humans (Group 2B) based on limited evidence for cancer in humans (specifically, for hepatocellular carcinoma, which is a type of liver cancer).¹² This classification places aspartame in the same category as hundreds of other substances, where evidence is limited and inconclusive. Importantly, IARC’s classification system identifies hazard potential rather than actual risk. IARC classifies aspartame as “possibly carcinogenic to humans” (Group 2B), based on limited evidence it might cause cancer (specifically liver cancer) in people. Despite this classification, the WHO’s Joint Expert Committee on Food Additives (JECFA) reaffirmed that the acceptable daily intake of 40 mg/kg body weight remains appropriate.

Non-Nutritive Sweeteners and Cancer Evidence

Early animal studies raised alarms about a possible link between certain NNS and cancer. However, extensive reviews and assessments by leading organizations provide reassurance:

• Animal Versus Human Studies: While some early studies in rats indicated that very high doses of NNS could lead to cancer¹³, later research and detailed reviews in humans found no clear evidence that the approved sweeteners cause cancer when consumed within the set ADI limits.
• Expert Reviews: Both the National Cancer Institute¹⁴ and MD Anderson Cancer Center¹⁵ state that, based on the current scientific evidence, there is no established link between consumption of the approved NNS and cancer risk in people who stick to recommended

Observational Studies

Recent large-scale observational research has produced mixed results. A notable French cohort study published in PLOS Medicine found that NNS (especially aspartame and acesulfame-K), which are used in many food and beverage brands worldwide, were associated with increased cancer risk.¹⁶ The study reported that enrolees consuming larger quantities of NNS, particularly aspartame and acesulfame-K, had a higher risk of overall cancer compared to non-consumers.

However, these findings must be interpreted cautiously as observational studies cannot establish causation and may be subject to confounding factors.

Meta-Analyses and Systematic Reviews

Comprehensive reviews of the literature present a more balanced perspective. Although multiple studies associate NNS with increased cancer risk, the majority of recent research data, including systematic reviews and meta-analyses, show no link between the use of NNS and cancer risk.^17,18 A large meta-analysis including 25 observational studies with 3,739,775 subjects concluded that the intake of sweeteners had no apparent association with overall cancer incidence and mortality.¹⁸

Current Position

While artificial sweeteners provide a low-calorie alternative to sugar, their long-term health effects remain a topic of ongoing research. Moderation and careful selection of sweeteners may help mitigate potential risks.

Current scientific evidence does not establish a clear causal relationship between NNS and cancer risk in humans. While some observational studies have suggested potential associations, particularly with aspartame, the overall body of evidence remains inconclusive and regulatory agencies continue to deem approved NNS safe for consumption at typical intake levels.

Based on the totality of available evidence, the scientific consensus supports the following position:

1. No Established Causal Link: Current evidence does not support a causal relationship between NNS consumption and cancer in humans.
2. IARC Classification Context: The “possibly carcinogenic” classification for aspartame reflects uncertainty rather than established risk and should not be interpreted as definitive evidence of carcinogenicity.
3. Regulatory Safety: Approved artificial sweeteners remain safe for consumption within established acceptable daily intake levels.
4. Research Gaps: More long-term prospective studies are needed to better characterize the effect of NNS on cancer risk.

Recommendations

Healthcare providers and public health officials should:

• Communicate that current evidence emphasizes that moderate consumption within regulatory guidelines appears safe
• Acknowledge uncertainty while avoiding unnecessary alarm
• Continue monitoring emerging research as the evidence base evolves
• Consider the individual factors when making dietary recommendations

Conclusion

While some studies have suggested potential associations between NNS and cancer risk, the current evidence base does not support definitive conclusions about causation. Regulatory agencies continue to maintain that approved sweeteners are safe for consumption at typical intake levels. Continued research and surveillance, integrating diverse methodologies, is needed to fully clarify the causal mechanisms and public health implications, and potential long-term health effects.

The SWEET Project has developed a Health Impact Database.¹⁹ This resource compiles human clinical trial data on various sweeteners and sweetness enhancers. It is designed to help researchers—and the interested public—gain a better understanding of the health effects associated with these compounds. You can explore the database and download the data here.

Reference list

1. European Food Safety Authority. Sweeteners. 2025. Accessed June 1, 2025. https://www.efsa.europa.eu/en/topics/topic/sweeteners
2. Chen Z, Wei C, Lamballais S, et al. Artificially sweetened beverage consumption and all-cause and cause-specific mortality: an updated systematic review and dose-response meta-analysis of prospective cohort studies. Nutr J. 2024;23(86):1-13. doi:10.1186/s12937-024-00985-7
3. Singh S, Kohli A, Trivedi S, et al. The contentious relationship between artificial sweeteners and cardiovascular health. Egypt J Intern Med. 2023;35(43):1-6. doi:10.1186/s43162-023-00232-1
4. Yin J, Zhu Y, Malik V, et al. Intake of Sugar-Sweetened and Low-Calorie Sweetened Beverages and Risk of Cardiovascular Disease: A Meta-Analysis and Systematic Review. Advances in Nutrition. 2021;12(1):89-101. doi:10.1093/ADVANCES/NMAA084
5. Ray S, Palui R. Artificial Sweeteners: Benefits, Risks and Controversy. Apollo Medicine. 2025;22(3):228-233. doi:10.1177/09760016251336000
6. Basson AR, Rodriguez-Palacios A, Cominelli F. Artificial Sweeteners: History and New Concepts on Inflammation. Front Nutr. 2021;8(746247):1-15. doi:10.3389/fnut.2021.746247
7. Cabral TM, Pereira MGB, Falchione AEZ, et al. Artificial Sweeteners as a Cause of Obesity: Weight Gain Mechanisms and Current Evidence. Health N Hav. 2018;10(05):700-717. doi:10.4236/health.2018.105054
8. Zhang Y, Tang Z, Shi Y, Li L. Associations between artificial sweetener intake from cereals, coffee, and tea and the risk of type 2 diabetes mellitus: A genetic correlation, mediation, and mendelian randomization analysis. PLoS One. 2024;19(2):1-15. doi:10.1371/journal.pone.0287496
9. Goveas LC. Artificial Sweeteners and the One Health crisis: Toxicity effects and Ecological consequences. Discover Applied Sciences. 2025;7(535). doi:10.1007/s42452-025-07107-w
10. World Health Organization. WHO advises not to use non-sugar sweeteners for weight control in newly released guideline. 2023. Accessed June 1, 2025. https://www.who.int/news/item/15-05-2023-who-advises-not-to-use-non-sugar-sweeteners-for-weight-control-in-newly-released-guideline
11. Harvard T.H. Chan School of Public Health. WHO Guidelines on Non-Sugar Sweeteners. 2023. Accessed June 1, 2025. https://nutritionsource.hsph.harvard.edu/2023/06/06/who-guidelines-non-sugar-sweeteners/
12. International Agency for Research on Cancer, World Health Organization. Aspartame hazard and risk assessment results released. 2023. Accessed April 1, 2025. : https://www.who.int/news/item/14-07-2023-aspartame-hazard-and-risk-assessment-results-released
13. Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M. Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environ Health Perspect. 2007;115(9):1293-1297. doi:10.1289/ehp.10271
14. National Cancer Institute. Artificial Sweeteners and Cancer. 2024. Accessed April 1, 2025. http://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet
15. MD Anderson Cancer Center. Artificial Sweeteners and Cancer: 7 Things to Know. 2023. Accessed June 1, 2025. https://www.mdanderson.org/cancerwise/artificial-sweeteners-and-cancer–7-things-to-know.h00-159620223.html
16. Debras C, Chazelas E, Srour B, et al. Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. PLoS Med. 2022;19(3):e1003950. doi:10.1371/journal.pmed.1003950
17. Ghusn W, Naik R, Yibirin M. The Impact of Artificial Sweeteners on Human Health and Cancer Association: A Comprehensive Clinical Review. doi:10.7759/cureus.51299
18. Yan S, Yan F, Liu L, Li B, Liu S, Cui W. Can Artificial Sweeteners Increase the Risk of Cancer Incidence and Mortality: Evidence from Prospective Studies. Nutrients. 2022;14(18):3742. doi:10.3390/NU14183742/S1
19. Scott CE, Stamataki N, Harrold JA, Raben A, Halford JCG. Health Impact Database Development for Sweeteners and Sweetness Enhancers: The SWEET Project. Nutr Bull. 2025;50(2):340-344. doi:10.1111/nbu.70006

This information sheet was written by Megan Pentz-Kluyts RD, B.Sc. Diet, M Nutrition, Nutrition and Dietetics Consultant to CANSA.

August 2025