A deep dive into the science behind your diet soda
For decades, artificial sweeteners have been heralded as the perfect solution for sugar reduction—offering the sweetness we crave without the calories we fear. Found in everything from diet sodas to yogurt, chewing gum to pharmaceuticals, these sugar substitutes have become ubiquitous in our modern food supply. Yet, beneath their sweet promise lies a pressing question that has haunted scientists and consumers alike: could these zero-calorie sweeteners come with a hidden cost, potentially increasing our risk of cancer? The answer, it turns out, is far more complex than a simple yes or no.
The relationship between artificial sweeteners and cancer is nuanced, with different sweeteners showing different effects and varying impacts based on consumption levels and individual factors.
Artificial sweeteners, also known as low-calorie sweeteners (LCS) or non-nutritive sweeteners (NNS), represent a broad category of sugar substitutes. These compounds are significantly sweeter than sugar—often hundreds to thousands of times sweeter—meaning only tiny amounts are needed to achieve the desired sweetness without adding substantial calories to our foods and beverages 1 .
Found in Diet Coke, Diet Pepsi, sugar-free gums
Used in Splenda and many diet products
The original Sweet'N Low
Derived from the stevia plant, but often highly processed
What makes this topic particularly challenging to study is that these compounds differ significantly in their chemical structures, how they're metabolized by our bodies, and their potential biological effects. Yet in nutritional research, they're often grouped together, making it difficult to pinpoint specific risks associated with individual sweeteners 1 .
When examining the relationship between artificial sweeteners and cancer, scientists rely heavily on meta-analyses—studies that combine and analyze data from multiple previous studies to identify overall trends. The most comprehensive analysis to date, published in September 2025 in Frontiers in Medicine, provides crucial insights 1 6 9 .
When all artificial sweeteners and all cancer types are considered together, there is no significant association between artificial sweetener consumption and overall cancer risk.
Pooled Relative Risk
This "umbrella review" examined 10 previous meta-analyses comprising 35 different datasets. The findings were surprisingly clear: when all artificial sweeteners and all cancer types are considered together, there is no significant association between artificial sweetener consumption and overall cancer risk 1 .
The pooled relative risk was 0.99, with a 95% confidence interval of 0.96–1.01. For non-statisticians, this essentially means that if the number 1.0 represents no effect, then 0.99 indicates a negligible effect—in this case, literally a 1% difference that isn't statistically significant 1 9 .
Data source: Meta-analysis of 10 previous studies 1
Increased risk
Among high consumers in specific cohorts
The consistency across different study designs was remarkable—whether researchers looked at prospective studies (RR: 1.00), case-control studies (RR: 0.94), or combined designs (RR: 0.96), the results consistently showed no significant association with cancer risk 1 .
One surprising finding emerged regarding gynecological cancers, where higher artificial sweetener intake was actually associated with a reduced risk (RR: 0.87). Similarly, a 2021 meta-analysis found artificial sweeteners inversely related to urinary system cancer risk in women (OR: 0.76) 1 5 . This doesn't necessarily mean artificial sweeteners protect against these cancers—the finding could reflect other lifestyle factors among sweetener users, or limitations in the observational data.
While the overall cancer risk may not be elevated, a groundbreaking 2025 study revealed a more nuanced and concerning picture—not about sweeteners causing cancer, but about how they might interfere with cancer treatment 3 .
Researchers found that sucralose consumption was linked to worse response to immunotherapy and poorer survival in patients with melanoma and non-small cell lung cancer.
The research team, led by Dr. Abby Overacre and Dr. Diwakar Davar, took a comprehensive approach:
They first examined 132 patients with advanced melanoma or non-small cell lung cancer who were receiving anti-PD1 immunotherapy. Patients completed detailed diet history questionnaires, including questions about artificial sweetener consumption 3 .
To establish causation, they turned to mouse models of adenocarcinoma and melanoma. Mice were fed sucralose in amounts comparable to human consumption (equivalent to one to two diet sodas daily) while receiving immunotherapy 3 .
The researchers then analyzed how sucralose was creating these effects, focusing on the gut microbiome and metabolic pathways 3 .
The findings were striking. Mice fed sucralose had significantly larger tumors and poorer survival when treated with immunotherapy. The mechanism traced back to the gut microbiome—sucralose shifted the composition of gut bacteria, increasing species that degrade arginine 3 .
Healthy gut microbiome with balanced arginine levels supporting effective T cell function.
Altered gut microbiome with reduced arginine levels, impairing T cell function and immunotherapy effectiveness.
Arginine is an amino acid essential for T cell function, particularly in cancer. "When arginine levels were depleted due to sucralose-driven shifts in the microbiome, T cells couldn't function properly," explained Overacre. "As a result, immunotherapy wasn't as effective" 3 .
Most remarkably, the researchers found they could counteract this effect. When they gave sucralose-fed mice arginine or citrulline (which converts to arginine in the body), the effectiveness of immunotherapy was restored 3 .
Based on study findings from Overacre & Davar (2025) 3
In July 2023, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) made waves when they classified aspartame as "possibly carcinogenic to humans" (Group 2B) 2 .
This classification sounds alarming, but understanding what it means requires context. The IARC classification indicates the strength of evidence about an agent's potential to cause cancer, not the actual risk at typical exposure levels 2 .
The "Group 2B" classification was based on "limited evidence" for carcinogenicity in humans—specifically for hepatocellular carcinoma (a type of liver cancer). There was also limited evidence for cancer in experimental animals and limited evidence related to possible mechanisms for causing cancer 2 .
Possibly Carcinogenic to Humans
This dual announcement highlights the crucial distinction between hazard (the potential to cause harm under any circumstances) and risk (the probability of harm occurring at specific exposure levels).
Simultaneously, the Joint Expert Committee on Food Additives (JECFA) reaffirmed the acceptable daily intake (ADI) for aspartame at 0-40 mg per kg of body weight. To put this in perspective, a 70kg (154lb) adult would need to consume more than 9-14 cans of diet soda daily to exceed this limit 2 .
Acceptable Daily Intake (ADI) for aspartame
Diet soda needed to exceed ADI for a 70kg adult
As Dr. Francesco Branca, WHO Director of Nutrition and Food Safety, explained: "The assessments of aspartame have indicated that, while safety is not a major concern at the doses which are commonly used, potential effects have been described that need to be investigated by more and better studies" 2 .
The evidence on artificial sweeteners and cancer reveals a complex picture with several key takeaways:
Different sweeteners may have different effects, and these effects may vary depending on individual factors like existing health conditions and gut microbiome composition 3 .
Most studies indicating potential harms looked at high consumption levels, while moderate use within acceptable daily intake levels appears generally safe for most people 2 .
If you have cancer or are undergoing treatment, discuss dietary sweetener use with your healthcare team, especially regarding immunotherapy 3 .
As Dr. Mary Schubauer-Berigan of the IARC Monographs programme noted, "The findings of limited evidence of carcinogenicity in humans and animals, and of limited mechanistic evidence on how carcinogenicity may occur, underscore the need for more research to refine our understanding" 2 .
The sweetener saga continues, reminding us that in nutrition science, simple answers are rare—but through ongoing research, we continue to move closer to the bittersweet truth.