Sugar substitute erythritol linked to elevated risk for blood clot formation
Click Here to Manage Email Alerts
Key takeaways:
- Erythritol, a common artificial sweetener, was linked to thrombotic risk in healthy volunteers.
- The nonnutritive sweetener is commonly found in chewing gum, jams and jellies, and sugar substitutes.
Erythritol, a nonnutritive sweetener generally recognized as safe by the FDA, demonstrated fast-acting prothrombotic properties not observed with traditional glucose in a small study.
In the FDA’s generally recognized as safe (GRAS) notice, erythritol is used as a flavor enhancer, formulation aid, nonnutritive sweetener in products including baked goods, breakfast cereals, chewing gum, jams and jellies, sugar substitutes and much more.
Stanley L. Hazen, MD, PhD, co-section head of preventive cardiology and chair of cardiovascular and metabolic sciences at the Cleveland Clinic Lerner Research Institute, and colleagues conducted an interventional study to assess the impact of erythritol intake compared with glucose on indices of platelet reactivity in healthy volunteers.
“Our earlier studies with erythritol showed in large-scale clinical observation studies that elevated blood erythritol levels were associated with incident risk of MI, stroke and death. Mechanistic studies — animal model, and blood based — all pointed to a prothrombotic effect with erythritol as the underlying mechanism,” Hazen, a Healio | Cardiology Today Editorial Board Member, told Healio.
As Healio previously reported, Marco Witkowski, MD, cardiologist and graduate student in Hazen’s laboratory at the Cleveland Clinic Lerner Research Institute, and Hazen had found associations between erythritol intake increased risk for heart attack and stroke.
Erythritol — which belongs to the family of sugar alcohols called polyols — occurs naturally in the human body, in small amounts, and can be found abundantly in grapes, mushrooms and fermented foods. Erythritol is the only polyol not made by reduction but by fermentation and is 60% to 80% as sweet as sucrose, according to data published in Applied Microbiology and Biotechnology.
“Later, studies with a related sugar alcohol — xylitol — showed similar patterns of clinical and mechanistic risks,” Hazen said. “Here, we wanted to both directly test in humans, comparing before vs. after ingestion in the subject. We also wanted to directly test in head-to-head comparison with a sugar-sweetened drink to see if glucose caused the same effects.”
In June, Hazen and colleagues published research in the European Heart Journal that indicated that xylitol, another low-calorie sugar substitute commonly found in gum and toothpaste, had prothrombotic properties, raising risk for major adverse CV events.
For their present analysis, published in Arteriosclerosis, Thrombosis, and Vascular Biology, the researchers conducted a prospective interventional study to evaluate the impact of erythritol intake compared with glucose consumption on indices of stimulus-dependent platelet reactivity in 20 healthy volunteers. The average age was about 30 years and nearly half were men.
All participants were nonsmokers without CVD, hypertension or diabetes, with normal renal function, no recent antiplatelet medication and no clinical history of bleeding, bruising or documented bleeding disorder.
Blood was drawn after an overnight fast and 30 minutes after intake of water mixed with 30 g erythritol or glucose. This quantity was based on levels found in common erythritol-sweetened foods and daily intake of some participants based on the 2013-2014 National Health and Nutrition Examination Survey and FDA documentation.
Hazen stated that diets high in erythritol may include “anything with artificial sweeteners in it. Erythritol is often used as a carrier for other artificial sweeteners because it looks like sugar, tastes like sugar and is, thus, often mixed with other artificial sweeteners.
“Processed foods, ranging from baking goods, condiments, drinks and many confectionaries, diabetes-safe labeled, keto-friendly or ‘low calorie’ all are foods often enriched in erythritol for enhanced sweetness without the calories,” he said.
For the analysis, plasma levels of erythritol and glucose were measured using liquid chromatography-mass spectrometry, and platelet function was evaluated using aggregometry and analysis of granule markers.
Among participants who drank the erythritol mixture, the researchers measured levels of circulating erythritol of more than 1,000-fold compared with baseline (median, 6,480 µmol/L vs. 3.8 µmol/L; P < .0001).
Among those who drank the glucose mixture, Hazen and colleagues observed similar erythritol levels compared with baseline, whereas glucose levels modestly increased (87 mg/dL vs. 127 mg/dL; P = .002).
Moreover, the researchers recorded significantly increased stimulus-dependent release of the platelet-dense granule marker serotonin and platelet alpha-granule marker CXCL4 in participants who consumed erythritol, whereas glucose intake conferred no significant change in stimulus-dependent release of serotonin or CXCL4.
“This to me makes it very clear glucose is a safer alternative,” Hazen told Healio. “This paper adds to that growing cumulative body of work [and] — with multiple different approaches and different methods — all point to concern with use of erythritol as an artificial sweetener.
“I am recommending to all of my patients, if your loved one has heart disease especially, I strongly recommend you advise them to avoid erythritol, xylitol and other sugar alcohols,” he said.
The researchers noted that a limitation of this study was the absence of long-term analysis of change in platelet function after erythritol intake. Previous research showed that erythritol is rapidly absorbed, with elevated plasma levels within 15 minutes, and data on the effects of chronic erythritol intake are needed.
For more information:
Stanley Hazen, MD, PhD, can be reached at 9500 Euclid Ave., Mail Code NC-I O, Cleveland, OH 44195.
References:
- Artificial sweetener erythritol’s major health risks. https://health.clevelandclinic.org/erythritol. Published March 7, 2023. Accessed Aug. 7, 2024.
- Cleveland Clinic study adds to increasing evidence that sugar substitute erythritol raises cardiovascular risk. Link. Published Aug 8, 2024. Accessed Aug. 8, 2024.
- FDA. GRAS Notices: GRN No. 789, Erythritol. https://cfsanappsexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&id=789. Last updated Aug. 2, 2024. Accessed Aug. 7, 2024.
- Regnat K, et al. Appl Microbiol Biotechnol. 2018;doi:10.1007/s00253-017-8654-1.
- Witkowski M, et al. Nat Med. 2023;doi:10.1038/s41591-023-02223-9.
Collapse
Click Here to Manage Email Alerts