Erythritol and Heart Health: Is Your Favorite Low-Calorie Sweetener Putting You at Risk

Low-calorie sweeteners, also known as LCS or artificial sweeteners, are sugar substitutes that are used in a wide variety of foods and beverages such as frozen desserts, yogurt, candies, baked goods, chewing gum, breakfast cereals, gelatins, and puddings. LCS are designed to provide sweetness without the added calories of sugar, making them a popular choice for people who want to reduce their calorie or sugar intake, or to better manage their blood glucose levels, especially those with diabetes or prediabetes.

Low-Calorie Sweeteners

The U.S. Food and Drug Administration (FDA) has approved six LCS as food additives, including aspartame, saccharin, acesulfame potassium, sucralose, neotame, and advantame. These LCS are all sweeter than table sugar, but contain few or no calories.

In addition to the six low-calorie sweeteners approved as food additives by the FDA, two other LCS are permitted for specific conditions of use in the food supply through the FDA’s GRAS (“Generally Recognized as Safe”) notification program.

The first is certain Steviol Glycosides, which come from the Stevia plant, Stevia rebaudiana, native to South America. Steviol glycosides are found in foods and beverages in the U.S. under various names, including Rebaudioside A (or Reb A), Stevioside, Rebaudioside D, or steviol glycoside mixtures that contain Rebaudioside A and/or Stevioside as the main ingredients. Some commercial brand names include Truvia® and PureVia®. At 200-400 times sweeter than sugar, the Acceptable Daily Intake is 9 packets daily. However, it is important to note that Stevia leaf and unrefined stevia extracts are not considered GRAS and are not allowed in the U.S. for use as sweeteners.

The second LCS is Monk Fruit, also known as luo han guo or Siraitia grosvenorii Swingle fruit extract (SGFE), which comes from a plant native to Southern China. Monk fruit is 100-250 times sweeter than sugar, but an Acceptable Daily Intake has not yet been determined.

It is worth noting that while LCS can be a useful tool for reducing calorie or sugar intake, it is important to consume them in moderation and to make informed choices based on personal health needs and preferences. Furthermore, their long-term effects on health are still uncertain and some people may experience digestive issues when consuming these sweeteners.

Sugar Alcohols

Sugar alcohols, also known as polyols, are a type of sweetener that have slightly fewer calories than table sugar. They are not classified as low-calorie sweeteners, but their sweetness varies from 25-100% as sweet as sugar. Unlike sugar, sugar alcohols do not promote tooth decay or cause sharp rises in blood glucose levels. Common examples of sugar alcohols include sorbitol, xylitol, lactitol, mannitol, erythritol, and maltitol. These sugar alcohols can be found in sugar-free candies, cookies, ice cream, beverages, and chewing gums. They are also used in toothpaste and medicines such as cough syrups.

However, consuming high quantities of certain sugar alcohols may cause digestive issues such as loose stools or diarrhea in some people. This is because sugar alcohols are absorbed slowly and can draw extra water into the intestines. With continued use, people may improve their tolerance to sugar alcohols. Erythritol is an exception because it is generally well-tolerated in most people, even when eaten in larger amounts.

Low-Calorie Sweeteners and Health

A 14-year follow-up in the French prospective Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l’Education Nationale–European Prospective Investigation into Cancer and Nutrition cohort looked at the association between self-reported consumption of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and 100% fruit juice with type 2 diabetes (T2D) risk. The study found that both SSB and ASB consumption were associated with an increased risk of T2D, with the highest quartiles of consumption having the highest risk. The study suggests that randomized trials are required to prove a causal link between ASB consumption and T2D.

A 2015 systematic review and meta-analysis aimed to investigate the association between the consumption of sugar-sweetened beverages, artificially sweetened beverages, and fruit juice with the risk of developing type 2 diabetes. The study analyzed 17 cohorts comprising 38,253 cases and 10,126,754 person-years of follow-up. The results showed positive associations with the incidence of type 2 diabetes. However, the authors did note that there could have been publication bias and confounding.

The NutriNet-Santé study in 2022 was a population-based prospective cohort study aimed to examine the associations between artificial sweeteners consumption from all dietary sources and the risk of cardiovascular diseases, overall and by molecule. A total of 103,388 participants were included in the study. The results showed that total artificial sweetener intake was associated with an increased risk of cardiovascular diseases by 9%, particularly cerebrovascular disease risk. Aspartame intake was associated with an increased risk of cerebrovascular events by 17%. Acesulfame potassium and sucralose were associated with increased coronary heart disease risk by 40%. The study suggests a potential direct association between higher artificial sweetener consumption and increased cardiovascular disease risk.

In a cell published in Cell 2022, researchers conducted a randomized controlled trial with 120 healthy adults to evaluate the short-term effects of four non-nutritive sweeteners (NNS) on the human microbiome, glucose tolerance, and additional health parameters. The participants were given sachets of each NNS supplement, including aspartame, saccharin, sucralose, and stevia, three times a day for 14 days, with glucose as a bulking agent. The study found that the NNS altered the human intestinal and oral microbiome and that saccharin and sucralose, when taken with glucose as a vehicle, resulted in elevated glycemia. The study suggests that commonly consumed NNS may not be physiologically inert and could affect the human microbiome in several distinct configurations.

Erythritol

Now let’s turn our attention to erythritol. Erythritol, a commonly used artificial sweetener found in many processed and "keto-related" foods, is considered safe by the US Food and Drug Administration under the designation of "generally recognized as safe" (GRAS). However, since there is no requirement for long-term safety studies, the potential long-term health effects of erythritol are not well understood.

Erythritol is a naturally occurring substance found in small amounts in fruits and vegetables. However, the artificial sweetener version of erythritol, which is derived from corn, is only 70% as sweet as sugar. Once consumed, it is poorly metabolized and mostly excreted in urine, which is why it is labeled as a "non-nutritive," "zero calories," or "natural" sweetener. It is expected to increase in popularity and double its market share in the sweetener industry within the next 5 years.

In a new study published in Nature Medicine, the authors did a three-part study. In the first part, the researchers found that polyols, including erythritol, were associated with major adverse cardiovascular events (MACE) in a group of 1157 patients.

In the second part, a validation cohort of 2149 patients in the US was studied over a 3-year period. Those with the highest levels of erythritol in their plasma had a 1.8-fold higher risk of MACE (major adverse cardiovascular events) compared to those with the lowest levels. This was after considering other cardiovascular risk factors.

In the European validation cohort, 833 patients were followed up for three years. Those with the highest quartile plasma levels of erythritol had a 2.21 times greater risk of MACE than those with lower levels (P = .010), after adjusting for confounding factors.

The researchers also found that erythritol at normal physiologic levels increased platelet activity and the formation of blood clots.

Finally, in a prospective study, eight healthy volunteers who consumed 30g of an erythritol-sweetened drink, which is equivalent to a can of commercially available beverage or a pint of keto ice cream, experienced significant and long-lasting increases (>2 days) in plasma erythritol levels.

It is important to note that our bodies do produce erythritol but in very low amounts.

Bottom line is that while sweeteners like erythritol have gained popularity as low-calorie alternatives, there is a pressing need for more comprehensive research into their long-term effects. As cardiovascular disease develops gradually over time and is the leading cause of death worldwide, it is essential to ensure that the foods we consume do not contain hidden contributors to heart disease. It is critical to maintain a balanced and healthy diet and make informed choices regarding sweeteners and other additives in our food.

References:

• Fagherazzi G, Vilier A, Saes Sartorelli D, Lajous M, Balkau B, Clavel-Chapelon F. Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l’Education Nationale–European Prospective Investigation into Cancer and Nutrition cohort–. The American journal of clinical nutrition. 2013 Jan 30;97(3):517-23.

• Imamura F, O’connor L, Ye Z, Mursu J, Hayashino Y, Bhupathiraju SN, Forouhi NG. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Br J Sports Med. 20

• Suez, J. et al. (2022) "Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance", Cell. doi: 10.1016/j.cell.2022.07.016. https://www.cell.com/cell/fulltext/S0092-8674(22)00919-916 Apr 1;50(8):496-504.

• Debras C. et al. Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. PLoS Med. 2022 Mar 24;19(3):e1003950. doi: 10.1371/journal.pmed.1003950. PMID: 35324894; PMCID: PMC8946744.

• Witkowski, M., Nemet, I., Alamri, H. et al. The artificial sweetener erythritol and cardiovascular event risk. Nat Med (2023). https://doi.org/10.1038/s41591-023-02223-9