Artificial Sweeteners and Cancer
What are artificial sweeteners?
Artificial sweeteners, also called sugar substitutes, nonnutritive sweeteners, or high-intensity sweeteners, are chemically synthesized substances that are used instead of sucrose (table sugar) to sweeten foods and beverages.
Because artificial sweeteners are many times sweeter than table sugar, much smaller amounts (200 to 20,000 times less) are needed to create the same level of sweetness. The caloric content of sweeteners used in such tiny amounts is negligible, which is why they are sometimes described as nonnutritive.
Six artificial sweeteners are approved as food additives by the US Food and Drug Administration (FDA): saccharin, aspartame, acesulfame potassium (acesulfame-K, or Ace-K), sucralose, neotame, and advantame. Before approving these sweeteners, FDA reviewed numerous safety studies that were conducted on each sweetener to identify possible health harms. The results of these studies showed no evidence that these sweeteners cause cancer or other harms in people.
In addition, FDA considers three plant- or fruit-based high-intensity sweeteners to be generally recognized as safe for use as sweeteners in the United States: stevia, luo han guo (also known as Swingle fruit or monk fruit extract), and thaumatin.
Do animal studies suggest a possible association between artificial sweeteners and cancer?
Concerns about artificial sweeteners and cancer initially arose when early studies linked the combination of cyclamate plus saccharin (and, to a lesser extent, cyclamate alone) with the development of bladder cancer in laboratory animals, particularly male rats.
As a result of these findings, cyclamate was banned in the United States in 1969. Although later reviews of those experimental data and evaluation of additional data led scientists to conclude that cyclamate does not cause cancer, it has not been reapproved in the United States (although it is approved in many other countries).
Laboratory studies have also linked saccharin at high doses with the development of bladder cancer in rats, and in 1981 saccharin was listed in the US National Toxicology Program’s Report on Carcinogens as a substance reasonably anticipated to be a human carcinogen. However, mechanistic studies (studies that examine how a substance works in the body) have shown that the ways in which saccharin causes cancer in rats do not apply in humans, and in 2000 it was removed from the list (for more information on the delisting of saccharin, see the Report on Carcinogens, Fifteenth Edition).
Most studies of the other five approved artificial sweeteners have provided no evidence that they cause cancer or other adverse health effects in lab animals. In 2019, an advisory group of 29 scientists from 18 countries gave aspartame a high priority for review by the International Agency for Research on Cancer Monographs program during 2020–2024 (1).
What have studies shown about possible associations between specific artificial sweeteners and cancer in people?
Epidemiologic studies (studies of patterns, causes, and control of diseases in groups of people) have examined possible associations between intakes of artificial sweeteners and risks of several cancers in people. It is important to keep in mind that studies of this type cannot establish cause-and-effect relationships because factors other than artificial sweetener use may potentially explain observed associations. However, these studies can provide important insights that can then be investigated in additional studies that can give more definitive answers.
Most epidemiologic studies have used consumption of artificially sweetened beverages as a proxy for (that is, a way for researchers to estimate) artificial sweetener intake. Such studies have not found evidence linking artificially sweetened beverage consumption with cancer in people (2, 3).
Only a few studies have assessed artificial sweetener intake from all dietary sources instead of using one dietary source as a proxy for total intake. In 2022, one such study—the web-based NutriNet-Santé cohort study—reported cancer incidence for more than 102,000 French adults who completed, multiple times during the study, 24-hour dietary records that included the names and brands of all commercial food products they consumed (4). Those detailed dietary records allowed the researchers to estimate the total intake of all artificial sweeteners combined.
After a median follow-up of about 8 years, those who consumed artificial sweeteners were slightly more likely to develop cancer overall than those who didn’t consume artificial sweeteners (4). In particular, people who consumed higher amounts of all artificial sweeteners combined were 1.13 times as likely to develop cancer overall as those who did not consume artificial sweeteners.
Because some studies have suggested that artificial sweeteners are associated with obesity, and obesity is in turn linked to at least 13 types of cancer, the NutriNet-Santé investigators also looked for associations between artificial sweetener intake and obesity-related cancers as a group. The risk of obesity-related cancers was increased to a similar extent (1.13 fold) as the risk of all cancers in people who consumed higher amounts of all artificial sweeteners compared with those who did not consume artificial sweeteners.
Many epidemiologic studies have been carried out to investigate whether saccharin is associated with bladder cancer incidence, given the findings in rats, but no clear evidence for such an association in humans has emerged. The results of these human studies contributed to the delisting of saccharin from the Report on Carcinogens.
In 2006, NCI researchers published an analysis of data from the NIH-AARP Diet and Health Study, which asked more than half a million US retirees to report their consumption of four aspartame-containing beverages during the past year on a questionnaire. Higher consumption of aspartame-containing beverages was not associated with the development of lymphoma, leukemia, or brain cancer during more than 5 years of follow-up (5).
A 2013 review of the epidemiologic evidence published between January 1990 and November 2012 also found no consistent association between the use of aspartame and cancer risk (6).
In 2022, the NutriNet-Santé cohort study reported that adults who consumed higher amounts of aspartame were slightly more likely to develop cancer overall (1.15 times the risk), breast cancer (1.22 times the risk), and obesity-related cancers (1.15 times the risk) than those who did not consume aspartame (4).
A range of studies have found no evidence that sucralose causes cancer in humans (7). In the NutriNet-Santé cohort study, sucralose intake was not associated with the risk of cancer (4).
The NutriNet-Santé cohort study reported that adults who consumed acesulfame-K had 1.13 times the risk of cancer overall as those who did not consume acesulfame-K (4). No other studies have examined whether acesulfame-K is associated with cancer in people.
Neotame and advantame
Neotame and advantame are derived from aspartame. No studies have reported on human cancer risks associated with either of these artificial sweeteners.
Do artificial sweeteners contribute to/play a role in obesity?
People may use artificial sweeteners to reduce the total calories they consume in their diet as part of an effort to avoid overweight and obesity, which have been linked to at least 13 types of cancer. Concerns have been raised that some artificial sweeteners might increase obesity, potentially having an indirect effect on cancer risk, although the findings are mixed (8). For example, in a small randomized clinical trial of adults with overweight or obesity, participants who drank beverages containing sucrose or saccharin had a significant increase in body weight compared with those who drank beverages containing aspartame, rebA (highly purified stevia), or sucralose (9). However, a systematic review and meta-analysis of 17 randomized controlled trials in adults found that substituting low- and no-calorie sweetened beverages for sugar-sweetened beverages was associated with small improvements in body weight (10).