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Longevity Briefs: ‘Keto Friendly’ Artificial Sweetener May Increase Risk Of Blood Clots

Posted on 8 March 2023

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Artificial sweeteners have long been favoured and marketed as a healthier alternative to sugar for people who wanted to manage their weight. While artificial sweeteners may contain little to no calories, mounting evidence suggests that they are anything but harmless, and some may not even be much healthier than sugar. Despite this controversy, artificial sweeteners remain popular among many consumers, and research on their safety continues. Scientists still don’t fully understand why artificial sweeteners can increase the risk of certain diseases.

What did the researchers do: In this study, researchers looked at the blood of patients whose health was being assessed for risk factors prior to cardiac surgery. Data came from 4139 patients in total across three independent cohorts in the United States and in Europe. Researchers looked at participants’ blood levels of erythritol, a natural plant-derived artificial sweetener, and studied the incidence of stroke and heart attack over the following three years.

Researchers also looked at the effects of erythritol on blood in vitro (outside the body) as well as the effects of erythritol consumption in 8 participants.

Key takeaway(s) from this research:

  • Elevated blood erythritol concentration was associated with a significant increase in heart attack and stroke over the next 3 years.
  • Adding erythritol to blood made it easier for platelets to cause clotting, which could contribute to an increased risk of cardiovascular events.
  • When healthy subjects consumed erythritol, this led to an increase in blood erythritol that  would have been sufficient to facilitate clotting based on the previous experiments.
  • After controlling for confounding factors, participants with higher blood concentrations of erythritol suffered a significantly higher rate of stroke and heart attack over the next 3 years. When researchers compared the 25% of patients with the lowest erythritol levels to the 25% with the highest levels, they found that risk of cardiovascular events roughly doubled for the highest 25%.
Left: % of participants from the larger US cohort surviving within 3 years of initial measurement for each quartile (Q1 are the 25% of participants with the lowest erythritol levels, Q2 are the next 25% and so on). Right: Hazard ratios for each quartile (molar concentration range shown in brackets) before adjustment (black) and after adjustment for confounding factors (red). Hazard ratio is the probability of a major adverse cardiovascular event (MACE) relative to the first quartile. Thus a hazard ratio of two would mean double the probability of a cardiovascular event when compared to the first quartile.
The artificial sweetener erythritol and cardiovascular event risk

When researchers exposed human platelets to levels of erythritol similar to those observed in patients’ blood, they found that the sweetener increased platelet aggregation, which is important for the formation of blood clots. This effect was also observed in mice with injured arteries. Finally, researchers gave 8 healthy human participants an equivalent dose of erythritol to that which might be found in a commercially available drink, and measured how it affected erythritol in their blood. They found that blood erythritol levels remained elevated for at least two days after consumption, and that these levels were above what would be necessary for an increase in platelet aggregation.

Since the relationship between erythritol and cardiovascular events is observational, it doesn’t prove that erythritol is dangerous – people who consume more of it could simply be more unhealthy in other ways that are hard to control for. Also keep in mind that these were people already undergoing risk assessment for heart surgery, so they represent a population that is more at risk of cardiovascular events than normal. The small amounts of erythritol found in some plants probably aren’t a significant concern, but given that many zero calorie and ‘keto friendly’ foods and beverages contain high quantities of erythritol, these associations need to be further investigated in both healthy and at-risk people.

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