Aspartame decreases fat deposits in mice at a cost of mild cardiac hypertrophy and reduced cognitive performance

Biomed Pharmacother. 2026 Jan:194:118891. doi: 10.1016/j.biopha.2025.118891. Epub 2025 Dec 12.

Abstract

Artificial sweeteners, such as aspartame, are widely used to reduce sugar intake to control body weight; however, their long-term metabolic and behavioral effects are unknown. To assess the long-term consequences, we evaluated the systemic effects of aspartame administration in male C57BL/6 mice over the course of one year, exposing them to a dose equivalent to one-sixth of the recommended maximum human daily intake. At this low dose, mice receiving aspartame showed decreased body weight, owing principally to a 20 % reduction in fat deposits, and this was associated with mild cardiac hypertrophy measured by MRI and histology, together with signs of altered neurobehavior, determined by the Barnes maze test. These findings indicate that while aspartame can help to achieve weight loss in mice, this is accompanied by pathophysiological changes in the heart and possibly in the brain. Thus, the study demonstrates that long-term exposure to artificial sweeteners can have a detrimental impact on organ function even at low doses, which suggests that current consumption guidelines should be critically re-examined.

Keywords: Artificial sweetener; Aspartame; Cardiac dysfunction; Cardiac magnetic resonance; Cognitive impairment; Weight loss.

MeSH terms

  • Adipose Tissue* / drug effects
  • Adipose Tissue* / metabolism
  • Animals
  • Aspartame* / adverse effects
  • Aspartame* / pharmacology
  • Body Weight / drug effects
  • Cardiomegaly* / chemically induced
  • Cardiomegaly* / pathology
  • Cardiomegaly* / physiopathology
  • Cognition* / drug effects
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Sweetening Agents* / pharmacology

Substances

  • Aspartame
  • Sweetening Agents