# No Evidence of Metabolomic Disruptions From Real‐World Intakes of Aspartame or Saccharin: The Coronary Artery Risk Development in Young Adults Study

## TL;DR

This study found no evidence that typical consumption of aspartame or saccharin disrupts metabolism in adults.

## Contribution

The study is the largest metabolomics analysis to date on real-world artificial sweetener intake and metabolism.

## Key findings

- Heavy aspartame intake was linked to caffeine and saccharin metabolite levels, but not to broader metabolic disruptions.
- Saccharin intake was only associated with its own plasma levels, not with other metabolites.
- No significant metabolic disruptions were observed for either sweetener at typical consumption levels.

## Abstract

Artificial sweeteners have become ubiquitous additives in the food supply, and yet the safety of their regular consumption remains controversial. The present study examined whether intakes of aspartame or saccharin are related to aberrations in the plasma metabolome indicating disruptions in metabolism.

A cohort of 2160 male and female participants, mean age 32.1 years, was included in the analysis. Liquid chromatography and mass‐spectrometry assessed 549 unique plasma metabolites. Diet was assessed using a validated questionnaire that allowed for estimation of aspartame and saccharin intakes. A generalized linear regression model evaluated associations of saccharin or aspartame intake with plasma metabolites with adjustment for potential confounders and multiple comparisons. Multiple sensitivity analyses and propensity score matching were conducted.

Heavy aspartame intake (≥ 5 servings/day) was associated with plasma levels (per SD) of saccharin (β = 0.90; q = 9.0E‐36), myo‐inositol (β = 0.27; q = 3.7E‐04), caffeine (β = 0.31; q = 4.1E‐04), and five metabolites of caffeine including 1,7‐dimethyluric acid (β = 0.37; q = 7.1E‐06), 1‐methylurate (β = 0.36; q = 7.1E‐06), 5‐acetylamino‐6‐amino‐3‐methyluracil (β = 0.38; q = 3.2E‐6), theophylline (β = 0.36; q = 9.1E‐06), and 1‐methylxanthine (β = 0.32; q = 2.0E‐03). Saccharin intake was associated with plasma levels of saccharin alone (β = 0.29; q = 1.8E‐10). No associations with sugars, carbohydrates, lipids, amino acids, or other metabolites that would suggest metabolic perturbations were observed with either artificial sweetener; sensitivity analyses supported these findings.

In the largest metabolomics study to date, no link was found between metabolic disruptions and either aspartame or saccharin intake. We cannot exclude the possibility that more extreme intakes may be related to metabolic disruptions among consumers of artificial sweeteners.

Consumption of aspartame or saccharin was not significantly related to plasma apart from caffeine metabolites. These findings do not support a link between real‐world intakes of aspartame or saccharin and metabolic disruptions; this has implications for treating physicians and patients concerned about artificial sweeteners.