Does Erythritol Consumption Add to Cardiovascular Risk?
Posted:
2023-03-29
What’s happening?
A
recent study examined erythritol and the risk of atherothrombotic disease (1). Erythritol is a sugar alcohol widely used as a low calorie sweetener in calorie-reduced foods, candies and baked goods (2). It is permitted for sale as a table-top sweetener and as a sweetener in certain types of beverages in Australia (3), Canada (4) and the United Kingdom (5). Erythritol is also naturally present in some fruits (e.g. melon, pear, grapes) and in fermented foods (e.g. cheese, soy sauce) and is produced in small amounts in our body (2).
It has gained increased appeal for use in food production as an artificial sweetener to address the prevalence of chronic diseases at the population level, like type 2 diabetes and cardiovascular diseases (CVD) (1). There is also an increased presence of erythritol in the market because of its commercial use in preparing keto-related foods, which continues to trend (6). As compared to other sugar alcohols, erythritol does not have an aftertaste, is absorbed in the body and is excreted unmodified in the urine so it does not raise blood glucose levels, and has less of a laxative effect (2).
Study analysis - strengths and weaknesses
The authors report on several investigations (1). The first study was an untargeted metabolomic discovery study of 1,157 patients undergoing elective diagnostic cardiac evaluation. Over three years, the risk for Major Adverse Cardiovascular Events (MACE; death, myocardial infarction and stroke) was associated with higher baseline plasma polyol levels (with erythritol being at the top).
The second study sought to validate this finding in two independent cohorts (n=2,149 U.S.; n=833, European) enrolled from large catchment areas with a high prevalence of CVD and risk factor burden, including type 2 diabetes and obesity. This analysis found that compared with participants in the lowest quartile of erythritol levels, those in the highest quartile had a substantially increased MACE risk (U.S. Cohort: adjusted HR (95%CI) 1.80 (1.18-2.77) and European cohort: 2.21 (1.20-4.07)).
Next, the authors examined a potential mechanism for erythritol’s contribution to CVD in vitro and identified that elevated erythritol levels (~45 micromolar) directly contributed to higher rates of clot formation and thrombosis risk. Finally, to examine the plasma response to consuming erythritol, a pilot intervention study in healthy volunteers (n=8) measured postprandial erythritol levels following consumption of an erythritol-sweetened drink (30 g - which the study authors compare to a single can of commercially available artificially-sweetened beverage or a pint of keto ice cream). This showed that blood levels were remarkably elevated (over 45 micromolar) within 30 minutes and remained elevated up to two days after consumption.
The study authors recommended examining the long-term effects of artificial sweeteners in general, and erythritol specifically, on CVD-related risks, particularly with populations who are at higher risk of CVD. The authors also noted the concern is compounded in that artificial sweeteners are marketed towards those typically at increased risk for future CVD events (i.e. persons living with diabetes, obesity or having a history of CVD and impaired kidney function).
Study strengths
- Association between incident adverse cardiovascular event risk occurred in both validation cohorts, independent of traditional CVD risk factors.
- The association remained significant in multiple different subgroups across both cohorts.
- Experimental evidence suggests a mechanism whereby elevated erythritol levels can contribute to increased cardiovascular risk.
- The consumption of erythritol does increase plasma levels in healthy volunteers, independent of endogenous erythritol production.
Study weaknesses
- The study design suggests a correlation but cannot confirm causation. Although adjustment was made for some risk factors, it is not possible to control for all possible confounding variables, including diet or exercise, and risk factors, including environmental and genetic.
- Dietary intake of erythritol was not examined in the cohorts. Levels of erythritol consumption in the pilot study (erythritol-sweetened drink containing 30 g in 300 mL water) may not reflect day-to-day consumption at the individual level.
- The measurement of erythritol was limited to one instance, as an overnight fasting level at the time of enrollment in the cohort studies; multiple measures may provide a better understanding of CVD risk.
- The application of findings is limited to individuals with a high prevalence of CVD and traditional risk factors, making it difficult to apply findings to the general population at this stage of research exploration.
- Clinical studies are needed to support or refute the possible associations described.
Now what?
Dietetic practitioners can continue to educate the public to eat a variety of foods including vegetables, fruit, whole grains and protein foods and to avoid eating too many foods with added sugars. For those who use sweeteners, advise to do so in moderation and that the ingestion of sugar alcohols may result in gastrointestinal symptoms, with erythritol possibly having less of an effect. Amounts recommended for safe consumption by the general public are based on country-specific regulations. Sugar alcohols approved for use include:
Sorbitol, sorbitol syrup, mannitol, isomalt, hydrogenated starch hydrolysates, maltitol, maltitol syrup, lactitol, xylitol and erythritol. Products that contain >10 g/100 g of sugar alcohol must include an advisory notice that excess consumption may have a laxative effect.
Sorbitol, sorbitol syrup, mannitol, isomalt, hydrogenated starch hydrolysates, maltitol, maltitol syrup, lactitol, xylitol and erythritol.
Sorbitol, sorbitol syrup, mannitol, isomalt, hydrogenated starch hydrolysates, maltitol, maltitol syrup, lactitol, xylitol and erythritol.
Legislation requires food labels of products containing >10% added sugar alcohols to include the statement “excessive consumption may produce laxative effects”.
The PEN Team will continue to review the literature and update the practice question recommendation on the safety of sweeteners related to cardiometabolic health as higher quality studies become available, as well as national guidelines that identify acceptable daily intakes.
Information from this study helps to address the inconclusiveness of the effect of sweeteners on cardiometabolic health.
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References
- Witkowski M, Nemet I, Alamri H, Wilcox J, Gupta N, Nimer N, Haghikia A, Li XS, Wu Y, Saha PP, Demuth I, König M, Steinhagen-Thiessen E, Cajka T, Fiehn O, Landmesser U, Tang WHW, Hazen SL. The artificial sweetener erythritol and cardiovascular event risk. Nat Med. 2023 Feb 27. doi: 10.1038/s41591-023-02223-9. Epub ahead of print. PMID: 36849732. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/36849732/
- Mazi TA, Stanhope KL. Erythritol: An In-Depth Discussion of Its Potential to Be a Beneficial Dietary Component. Nutrients. 2023 Jan 1;15(1):204. doi: 10.3390/nu15010204. PMID: 36615861; PMCID: PMC9824470. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/36615861/
- Food Standards Australia New Zealand. Intense Sweeteners. 2021. Available from: https://www.foodstandards.gov.au/consumer/additives/pages/sweeteners.aspx
- Government of Canada. Notice of Modification to the List of Permitted Sweeteners to Extend the Use of Erythritol to MEal Replacement Dry Beverage Mixes and to Nutritional Supplements in Various Formats (Bar, Instant Breakfast Cereal, and Hot and Cold Beverage Dry Mix) - Reference Number: NOM/ADM-0093. 2017. Available from: https://www.canada.ca/en/health-canada/services/food-nutrition/public-involvement-partnerships/notice-modification-list-permitted-sweeteners-extend-use-erythritol-meal-replacement-beverage-mixes-nutritional-supplements-various-formats-instant.html
- European Food Safety Authority. Scientific opinion on the safety of the proposed extension of use of erythritol (E 968) as a food additive. 2015. Available from: https://efsa.onlinelibrary.wiley.com/doi/pdfdirect/10.2903/j.efsa.2015.4033#:~:text=Erythritol%20(E%20968)%20is%20a,food%20categories%20at%20quantum%20satis.
- Shoup, ME. Keto, a long-lasting trend? New keto product launches double in past year. FoodNavigator USA. 2021. Available from: https://www.foodnavigator-usa.com/Article/2021/06/28/Keto-a-long-lasting-trend-New-keto-product-launches-double-in-past-yea