Association between Aspartame Consumption and Cancer Risk: Evidence from a Large Prospective Cohort

Aspartame, one of the most widely used low-calorie sweeteners, was recently classified by the International Agency for Research on Cancer as possibly carcinogenic to humans. Epidemiologic evidence remains inconsistent, particularly for specific and obesity-related cancers (ObCa), highlighting the need for further large prospective studies.

We examined the association between aspartame intake and risk of all cancers combined, non-ObCa, ObCa, and 2 ObCa subgroups (digestive and female reproductive), in the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC).

Among 100,004 U.S. adults (98% non-Hispanic White; mean age: 69 y), aspartame intake from low-calorie carbonated beverages (70‒180 mg per 12-oz serving depending on type) and single-serving packets (20 mg/packet) was assessed in 1999 and 2003 using a modified Willett food frequency questionnaire. Participants were categorized as nonconsumers (0 to less than once per month) or consumers (at least once per month). Total intake estimates were converted to daily equivalents, and consumers were further grouped into 3 categories: >0 to <20 mg/d, 20 to <80 mg/d, and ≥80 mg/d. A total of 21,356 cancer cases were verified, including 8087 ObCa (2976 digestive; 2756 female reproductive) through June 2017. Multivariable-adjusted Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) overall and by baseline weight status (overweight/obesity compared with under/normal weight).

At baseline, 74.3% of the participants were aspartame consumers. Compared with nonconsumers, consumers had higher risks of developing all cancers combined [adjusted HR (aHR): 1.13; 95% CI: 1.08, 1.18; P < 0.0001], non-ObCa (aHR: 1.10; 95% CI: 1.05, 1.16; P = 0.0003), ObCa (aHR: 1.17; 95% CI: 1.09, 1.26; P < 0.0001); digestive ObCa (aHR: 1.19; 95% CI: 1.06, 1.33; P = 0.004) and female reproductive ObCa (aHR: 1.13; 95% CI: 1.00, 1.28, P = 0.05). No clear dose-response relationship was observed for any of the cancer outcomes. Associations were not modified by weight status.

In the CPS-II NC, aspartame consumption is associated with higher cancer risk, including ObCa and non-ObCa, regardless of weight status. However, the lack of dose-response underscores the need for cautious interpretation and replication in future studies.