Erythritol

For nearly 20 years, I've been sharing information about artificial sweeteners. Over the next three weeks, I want to review some studies that have made major headlines and look at what the research actually shows versus what the news reports claimed.

In February 2023, headlines declared erythritol a "zero-calorie sweetener linked to heart attack and stroke." Researchers found that people with higher levels of erythritol in their blood were more likely to suffer heart attacks or strokes. That sounds alarming. But the details matter.

The study had a significant limitation. Researchers measured how much erythritol was circulating in subjects' plasma, but they didn't track how much erythritol those subjects were actually eating or drinking. That missing piece creates a serious problem for interpreting the results.

Here's why. Erythritol isn't only consumed in food and drink. The body also produces it naturally through the pentose phosphate pathway, particularly in response to oxidative stress and vascular damage. Because the body can produce erythritol under metabolic stress, elevated blood levels don't automatically tell us how much came from diet versus underlying disease.

Now look at the study population. More than 75 percent of subjects already had coronary artery disease. The average age was between 55 and 72, and the average BMI was 29.2, which is in the overweight range approaching obesity. These weren't healthy people. It's entirely plausible that their elevated plasma erythritol was at least partly a marker of existing disease rather than solely a product of what they were eating.

The researchers themselves acknowledged they couldn't establish causation. What the study found was an association, and associations in high-risk populations require careful interpretation.

That said, the Hazen study wasn't just an observational cohort. The same researchers also conducted laboratory experiments showing that erythritol promotes platelet aggregation, which is the clumping behavior that contributes to clot formation. That mechanistic finding adds biological plausibility to the concern, although mechanistic studies alone still can't establish real-world cardiovascular risk. The cardiovascular question around erythritol isn't settled science in either direction, and it deserves ongoing research rather than either panic or dismissal.

The responsible conclusion is that we need more research specifically tracking dietary erythritol intake in healthy populations. The headlines overstated what the study proved. But this isn't a case of pure junk science, either.

The Splenda Story

Then came the Splenda headlines. In June 2023, news organizations reported that a chemical found in Splenda "damages DNA," calling the finding "genotoxic." I got calls and emails from more than a dozen people asking whether Splenda was safe and whether they should stop using it.

The study, published in the Journal of Toxicology and Environmental Health, found that sucralose-6-acetate, a minor chemical byproduct associated with sucralose, increased expression of genes linked to inflammation, oxidative stress, and cancer in cell experiments. That sounds serious.

The phrase "cell experiments" is doing a lot of work in that sentence.

Researchers ran these tests in vitro, meaning on isolated cells in a petri dish, not in living humans or animals. Petri dish experiments are useful for generating hypotheses and identifying potential mechanisms. They're not evidence of what happens inside a human body, where absorption, metabolism, and elimination all change the picture substantially.

Here's the critical part. The concentrations of sucralose used in the petri dish were substantially higher than what actually circulates in human blood after drinking a sucralose-sweetened beverage. A 2017 study measured blood concentrations in people who consumed up to 250 milligrams of sucralose, the equivalent of about four diet sodas. Peak blood concentrations reached only 200 to 400 nanograms per milliliter. The petri dish experiments used concentrations far beyond that range.

The findings don't demonstrate that normal human consumption produces these effects, although further toxicology work examining long-term, real-world exposure may still be worthwhile. What the findings don't support is the headline that ran in news outlets across the country. This was a preliminary result, conducted at concentrations well above measured human plasma levels, that got reported as a direct consumer warning.

Oversimplified reporting like that can create unnecessary confusion about relative risk, and it can drive people away from products that help them reduce sugar intake based on evidence that doesn't apply to how those products are actually used.

In Part 2, I'll cover the aspartame and cancer story. In Part 3, I'll get into the real, documented concerns about artificial sweeteners, because there are several worth knowing about.

Part 1 2 3

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Reference Links:

The artificial sweetener erythritol and cardiovascular event risk

Marco Witkowski, Ina Nemet, Hassan Alamri, Jennifer Wilcox, Nilaksh Gupta, Nisreen Nimer, Arash Haghikia, Xinmin S. Li, Yuping Wu, Prasenjit Prasad Saha, Ilja Demuth, Maximilian König, Elisabeth Steinhagen-Thiessen, Tomas Cajka, Oliver Fiehn, Ulf Landmesser, W. H. Wilson Tang & Stanley L. Hazen
Nature Medicine, Published 27 February 2023

Click Here for the Study: https://www.nature.com/articles/s41591-023-02223-9

Erythritol synthesis is elevated in response to oxidative stress and regulated by the non-oxidative pentose phosphate pathway in A549 cells

Semira R. Ortiz1, Alexander Heinz2, Karsten Hiller2 and Martha S. Field1*
Frontiers in Nutrition, Published 06 October, 2022 - Volume 9 - 2022 | https://doi.org/10.3389/fnut.2022.953056

Click Here for the Study: https://www.frontiersin.org/articles/10.3389/fnut.2022.953056/full

Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays

Susan S. Schiffman, Elizabeth H. Scholl, Terrence S. Furey & H. Troy Nagle
Journal of Toxicology and Environmental Health, Published online: 29 May 2023

Click Here for the Study: https://doi.org/10.1080/10937404.2023.2213903

Development and Application of TK6-derived Cells Expressing Human Cytochrome P450s for Genotoxicity Testing

Xilin Li, Si Chen, Xiaoqing Guo, Qiangen Wu, Ji-Eun Seo, Lei Guo, Mugimane G Manjanatha, Tong Zhou, Kristine L Witt, Nan Mei
Toxicological Sciences: An Official Journal of the Society of Toxicology, Published 2020 Jun 1;175(2):251-265. doi: 10.1093/toxsci/kfaa035.

Click Here for the Study: https://doi.org/10.1093/toxsci/kfaa035

Plasma concentrations of sucralose in children and adults

Allison C. Sylvetsky,Viviana Bauman,Jenny E. Blau,H. Martin Garraffo,Peter J. Walter &Kristina I. Rother
STUDY JOURNAL, Published 06 June 2017 - Cite this as: BMJ 2017;357:j2353

Click Here for the Study: https://doi.org/10.1080/02772248.2016.1234754

Ten-Week Sucralose Consumption Induces Gut Dysbiosis and Altered Glucose and Insulin Levels in Healthy Young Adults

Lucía A. Méndez-García ,Nallely Bueno-Hernández, Miguel A. Cid-Soto, Karen L. De León, Viridiana M. Mendoza-Martínez, Aranza J. Espinosa-Flores, Miguel Carrero-Aguirre, Marcela Esquivel-Velázquez, Mireya León-Hernández, Rebeca Viurcos-Sanabria, Alejandra Ruíz-Barranco, Julián M. Cota-Arce, Angélica Álvarez-Lee, Marco A. De León-Nava, Guillermo Meléndez and Galileo Escobedo
Microorganisms, Published 14 February 2022

Click Here for the Study: https://doi.org/10.3390/microorganisms10020434

No Association between Low-Calorie Sweetener (LCS) Use and Overall Cancer Risk in the Nationally Representative Database in the US: Analyses of NHANES 1988–2018 Data and 2019 Public-Use Linked Mortality Files

Victor L. Fulgoni III and Adam Drewnowski
Nutrients, Published 22 November 2022

Click Here for the Study: https://doi.org/10.3390/nu14234957

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7/2/2023
Updated 5/26/2026