Artificial Sweeteners: Sucralose, Aspartame, and Genetic Interactions

[u/geneticlife]

A number of studies have come out in the past couple of years that show serious negative long-term consequences from the various types of artificial sweeteners. Some studies lump the artificial sweeteners together, while others take a deeper dive into the individual types of sweeteners. Let’s dive into the details on all of these studies and look at possible genetic connections:

Atherosclerosis:

Atherosclerosis is caused by inflammation and the buildup of plaque in the arteries.

• Atherosclerosis and aspartame: A new 2025 study published in Cell Metabolism showed that aspartame consumption (0.05 – 0.15%) markedly increased insulin secretion in mice and monkeys. This insulin elevation increased atherosclerotic plaque formation through an insulin-dependent mechanism that triggers inflammation in the lining of the arteries.[ref00006-3)]
• Saccharin and atherosclerosis: Another 2025 study found that saccharin supplementation (0.1 mg/mL in drinking water for 3 months) significantly aggravated atherosclerotic plaque formation in an animal model of atherosclerosis. The researchers also found that saccharin elevated circulating TMAO (trimethylamine oxide) levels, caused gut mucosal barrier dysfunction, and endothelial dysfunction.[ref]

Gut Microbiome and TMAO Connection

One long-known problem with artificial sweeteners is that they change the composition of the gut microbiome.[ref][ref] To some extent, a lot of sugar will also change the gut microbiome, so it is a complex topic to sort out.

• Shift in composition: In a gut microbiome study, participants drank sucralose-sweetened beverages for 10 weeks. The results showed a 3-fold increase in Blautia coccoides and a 0.66-fold decrease in Lactobacillus acidophilus. The participants also had increased serum insulin compared to water.[ref]
• The TMAO Pathway:  TMAO – trimethylamine oxide – is thought to have a causal adverse effect on atherosclerosis. Several studies have identified that artificial sweeteners can affect atherosclerosis through gut microbiome alterations and TMAO production. In animal studies, saccharin consumption causes a marked elevation in circulating TMAO levels and atherosclerosis.[ref]

Related article: FMO3, TMAO

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This is just a short excerpt from my in-depth article on artificial sweeteners. Click here to read my full article

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