Artificial Sweeteners and Chronic Disease Risk: A Scientific Review

Artificial sweeteners have been used in the United States since the early 20th century, beginning with the discovery of saccharin in the late 1800s and its widespread adoption during sugar shortages in World War I and II. Their popularity surged in the 1950s and 1960s with the rise of diet culture and concerns about sugar’s health effects, leading to the introduction of other non-nutritive sweeteners such as cyclamate, aspartame, and later sucralose. Despite safety controversies of artificial sweeteners and chronic disease, artificial sweeteners remain widely used in American diets today, appearing in everything from diet sodas to low-calorie snacks, with millions of consumers using them in the attempt to manage weight, blood sugar, or caloric intake.

Cardiovascular and Mortality Concerns

A comprehensive 2024 umbrella review published in Nutrition Reviews examined six meta-analyses ¹  linking artificially sweetened beverages to several concerning health outcomes. The review found associations with increased risk for all-cause mortality, stroke, coronary heart disease, hypertension, type 2 diabetes, metabolic syndrome, and leukemia. Interestingly, the analysis indicated a potential protective effect against colorectal cancer. Despite these findings, the authors emphasized that the magnitude of these associations was relatively modest.

Building on these concerns, a 2025 systematic review and meta-analysis published in Current Problems in Cardiology ² analyzed data from 12 prospective cohort studies encompassing over 1.2 million participants. The results were striking for regular consumers of artificially sweetened beverages (one or more daily):

• 29% elevated risk of cardiovascular mortality
• 15% increased risk of stroke incidence
• 14% higher all-cause mortality risk

Weight Management Paradox

Despite their zero or low-calorie profile, artificially sweetened beverages appear counterproductive for weight management. A longitudinal 2023 study in the International Journal of Obesity³ analyzed 20 years of data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Among 2,745 participants who began the study without obesity, those who regularly consumed diet beverages and artificial sweeteners demonstrated a higher risk of developing obesity over time.

The researchers documented approximately 8-15% greater volumes of body fat (visceral, intermuscular, and subcutaneous) among participants in the highest consumption quintile compared to those in the lowest quintile.

Potential Mechanisms

Recent research suggests several mechanisms that might explain these paradoxical associations. Artificial sweeteners may:

1. Disrupt gut microbiota composition, potentially altering glucose metabolism
2. Interfere with appetite regulation hormones, potentially increasing overall caloric intake
3. Trigger insulin responses through cephalic phase reactions (a sweet taste stimulating the release of insulin), despite containing no actual sugar
4. Maintain or reinforce preferences for sweet-tasting foods, leading to poor dietary choices.

Study Finds Link Between Diet Soda and Diabetes Risk

A recent large-scale study has uncovered an important connection between what we drink and our health. Researchers tracked the drinking habits of nearly 25,000 people for over 10 years to see who would develop diabetes.

The results confirmed what many health experts already suspected: people who regularly drank sugary sodas had a higher chance of developing type 2 diabetes over time.

But there’s more to the story than just sugar-sweetened beverages. The study provides valuable information about how different drinks might affect our long-term health ⁴.

Aspartame Promotes Insulin Resistance and Inflammation

Recent groundbreaking research by Wu et al. (2025) reveals a concerning link between the artificial sweetener aspartame and exacerbated atherosclerosis. This study demonstrates that aspartame consumption elevates insulin levels through parasympathetic activation, triggering an inflammatory cascade. Aspartame triggers inflammation in blood vessels by increasing levels of a molecule called CX3CL1, which happens with the help of insulin. This molecule sends signals through a pathway involving the CX3CR1 receptor. When scientists removed the gene for CX3CR1 in tests, the harmful effects of aspartame on the arteries disappeared. This suggests that blocking this pathway could help treat heart and brain diseases linked to atherosclerosis.⁵

A landmark French study involving 103,000 adults has revealed that aspartame, one of the most widely used artificial sweeteners, is associated with a 17% increased risk of cerebrovascular events. Published in the BMJ⁶, this large-scale prospective research challenges the perception of artificial sweeteners as safe alternatives to sugar, finding a 9% higher overall risk of cardiovascular disease among consumers.

Researchers from Sorbonne Paris Nord University tracked participants’ sweetener intake through detailed dietary records over approximately ten years, during which 1,502 cardiovascular events were documented. Their conclusion is clear: these additives, present in thousands of everyday foods and beverages within a $7.2 billion global market,“should not be considered a healthy and safe alternative to sugar” and represent a modifiable risk factor for cardiovascular disease prevention.

Artificial Sweeteners and Chronic Disease Risk and Cancer Risk: What to Make of Food Additive Warnings

When discussing cancer prevention, patients often ask about food additives and their potential risks. A recent example helps illustrate how to interpret cancer risk information.

In July 2023, the World Health Organization (WHO) classified aspartame—an artificial sweetener commonly found in diet sodas and low-calorie foods—as “possibly carcinogenic to humans.” ⁷ This announcement understandably raised concerns among many people.

What This Classification Actually Means

It’s important to understand that this classification doesn’t mean aspartame definitely causes cancer. Rather, it indicates there is limited evidence suggesting a potential link, specifically to liver cancer. The WHO placed aspartame in “Group 2B,” which means there’s some evidence but it’s not conclusive ⁸.

The WHO made an important distinction between:

• Hazard identification (the potential to cause harm)
• Risk assessment (the likelihood of harm at specific exposure levels)

Despite this classification, the WHO did not change its recommended daily limits for aspartame consumption. These remain at 40 mg per kilogram of body weight per day. For an average adult, this equals approximately 9-14 cans of diet soda daily—far more than most people consume. ⁹ 

These findings suggest artificially sweetened beverages should be avoided. While reducing refined sugar intake remains important, substituting with artificial sweeteners may not provide the expected health benefits and could potentially introduce other risks.

Potential Health Effects of Sucralose

Sucralose, a popular artificial sweetener, has sparked safety concerns and scientific debate, particularly regarding its impact on the gut microbiome, insulin metabolism, and immune system. A study of healthy young adults found that 10 weeks of sucralose consumption caused a greater insulin response and higher concentrations of insulin by the end of the study. ¹⁰ 

It follows that years of consumption could eventually lead to insulin resistance and metabolic syndrome. Some studies suggest that sucralose may alter the composition and diversity of gut bacteria, potentially disrupting the balance of beneficial microbes, which could influence digestion, metabolism, and overall health. Additionally, emerging research indicates that sucralose might trigger low-grade inflammation or affect immune function by interacting with specific cellular pathways. One study revealed that, “the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation.”  ¹¹ 

Regulatory agencies like the FDA and EFSA have deemed sucralose safe for general consumption, but critics argue that more long-term independent studies are needed to fully understand its biological effects, especially with chronic exposure. As scientific understanding evolves, consumers and healthcare providers are encouraged to stay informed and consider individual tolerance when using artificial sweeteners like sucralose. 

Conclusion

While artificial sweeteners were introduced as a healthier alternative to sugar, growing evidence suggests that they may come with their own set of health risks. Studies have linked regular use of artificial sweeteners like aspartame and sucralose to increased risks of obesity, heart disease, stroke, type 2 diabetes, and possibly even cancer. Research also shows that these sweeteners can affect the gut microbiome, disrupt insulin response, and cause inflammation— all factors that may contribute to chronic disease over time. Although agencies like the FDA continue to approve their use, many scientists and health professionals agree that more long-term, independent studies are needed. I believe it is always wise to limit consumption of synthetic chemicals and focus on whole, natural foods to enjoy true long-term health.