Erythritol: The Latest Research on Sugar Substitutes and Cardiovascular Risks

For years, erythritol has been a widely used sugar substitute in the low-carbohydrate and ketogenic communities. Marketed as a "natural" sugar alcohol with minimal impact on blood glucose levels, it has been an attractive choice for individuals managing diabetes, particularly those following therapeutic carbohydrate reduction (TCR) protocols for type 1 diabetes.

However, emerging research raises critical concerns about its safety, particularly regarding its role in promoting blood clot formation and cardiovascular risks.

Recent studies, including a paper by Choi et al. (2024) and a detailed video analysis by Dr. Nick Norwitz, have shed new light on the metabolic effects of erythritol, comparing it to allulose—a rare sugar that may offer a safer alternative. This article will explore the latest findings, the implications for individuals with type 1 diabetes, and whether allulose might be the better choice for maintaining stable blood glucose levels while mitigating potential health risks.

Erythritol and Cardiovascular Risks: What the Science Says

The study by Choi et al. (2024) investigated how erythritol and allulose affect platelet function, mitochondrial activity, and thrombosis risk. Their findings align with earlier research that linked erythritol to increased clotting potential, raising concerns about its safety in individuals with a predisposition to cardiovascular disease.

1. Erythritol and Blood Clots

One of the most alarming findings from Choi et al.'s (2024) research was that erythritol exacerbates platelet aggregation, a critical process in blood clot formation. The study examined the effects of erythritol in mice fed a high-fat, Western-style diet and found that it amplified the activation of genetic pathways related to platelet aggregation and thrombotic risk. This suggests that erythritol may play an active role in increasing clot formation rather than simply being a bystander marker of cardiovascular risk.

To further explore its potential pro-thrombotic effects, the researchers conducted a gene set enrichment analysis, comparing genetic pathways affected by erythritol with those observed in sickle cell disease (SCD)—a condition known for its high clotting risk. The results indicated that erythritol mirrored many of the pro-clotting pathways seen in sickle cell disease, a strong indication that its effects on platelet function could have real clinical consequences. Additionally, the study identified mitochondrial dysfunction as a possible mechanism through which erythritol exacerbates clotting risk. Specifically, erythritol was shown to downregulate key mitochondrial pathways involved in ATP synthesis and oxidative phosphorylation. Since mitochondrial dysfunction is closely linked to increased oxidative stress and platelet hyperactivity, this finding suggests that erythritol may promote an environment conducive to excessive clot formation.

These findings align with previous concerns raised by Witkowski et al. (2023), who observed a strong correlation between erythritol levels in the bloodstream and an increased risk of major adverse cardiovascular events (MACE). Their study found that erythritol promoted platelet activation, further supporting the hypothesis that it may contribute to an increased risk of thrombosis.

For individuals with type 1 diabetes, who already have a significantly higher risk of cardiovascular complications, these findings warrant serious consideration. Given that many individuals managing diabetes turn to erythritol-containing products as a sugar substitute to maintain glycemic control, it is crucial to weigh the metabolic benefits against the potential cardiovascular risks associated with its consumption.

2. Erythritol and Sickle Cell Disease Pathways

Choi et al. (2024) further examined erythritol’s impact on genetic pathways associated with sickle cell disease (SCD), a hereditary blood disorder known for its abnormal red blood cell morphology and increased risk of clot formation. SCD is characterized by chronic hemolysis, inflammation, and vascular dysfunction, all of which contribute to a pro-thrombotic state. By comparing gene expression profiles, the researchers found that erythritol activated many of the same pathways observed in individuals with SCD, raising concerns about its role in promoting excessive blood clotting.

The gene set enrichment analysis (GSEA) used in the study provided compelling evidence that erythritol is not merely correlated with clotting risk but may actively drive it. The analysis showed that several key pathways involved in platelet aggregation and vascular dysfunction were upregulated in both erythritol-treated mice and human SCD patients. This included pathways related to oxidative stress, endothelial dysfunction, and mitochondrial impairment, all of which are known contributors to thrombotic events.

A particularly concerning finding was that erythritol downregulated mitochondrial function, mirroring the disruptions seen in SCD. Mitochondria play a crucial role in regulating oxidative stress and cellular energy metabolism, both of which influence platelet activation and clot stability. By impairing ATP synthesis and mitochondrial respiration, erythritol may increase the vulnerability of blood cells to clotting triggers, similar to what occurs in SCD.

These results reinforce the idea that erythritol may not just be a passive marker of cardiovascular risk but an active participant in the biological processes that promote thrombosis. Given that SCD patients already face an elevated risk of strokes, heart disease, and vascular complications, the finding that erythritol mimics these harmful pathways raises concerns about its safety, particularly for individuals with preexisting clotting risks.

3. Erythritol and Mitochondrial Dysfunction

Mitochondria are essential for cellular energy production, playing a pivotal role in ATP synthesis, oxidative stress regulation, and overall metabolic function. Disruptions in mitochondrial pathways have been linked to numerous chronic conditions, including diabetes, cardiovascular disease, and metabolic dysfunction. In the study by Choi et al. (2024), erythritol was found to downregulate key mitochondrial pathways, particularly those involved in ATP synthesis and electron transport chain function.

This is significant because ATP (adenosine triphosphate) is the primary energy source for cells, and its production depends on a properly functioning electron transport chain (ETC). The study’s findings indicate that erythritol hinders ATP synthesis, which may contribute to increased oxidative stress and impaired cellular metabolism. These detrimental effects mirror those seen in metabolic disorders and chronic inflammatory diseases, raising concerns about erythritol’s broader impact on systemic health, beyond its role in clot formation.

The link between mitochondrial dysfunction and metabolic disease is well established.

Diabetes, insulin resistance, and cardiovascular disease are all associated with mitochondrial impairment, where cells struggle to efficiently produce energy and manage oxidative stress. The study’s findings align with previous research highlighting the role of mitochondrial dysfunction in diabetes, where reduced ATP production and increased oxidative stress are tied to worsening insulin sensitivity and higher cardiovascular risk.

Additionally, the study found similarities between the mitochondrial dysfunction caused by erythritol and that observed in sickle cell disease (SCD). SCD is characterized by elevated oxidative stress, chronic inflammation, and vascular complications, all of which are exacerbated by mitochondrial inefficiencies. By disrupting mitochondrial function, erythritol appears to parallel these harmful pathways, further implicating it as a potential contributor to metabolic and vascular dysfunction.

Given the importance of mitochondria in metabolic health, these findings suggest that erythritol’s effects extend beyond blood clotting and may contribute to a broader spectrum of metabolic and inflammatory diseases. For individuals already at risk—such as those with type 1 diabetes, insulin resistance, or cardiovascular disease—this raises serious concerns about the widespread use of erythritol as a sugar substitute.

The Case for Allulose: A Safer Alternative?

Allulose, a rare sugar with a molecular structure similar to fructose, has been gaining attention as a potential alternative to erythritol. Unlike erythritol, which exacerbated thrombotic pathways, allulose was found to reduce platelet aggregation and improve mitochondrial function.

1. Allulose and Reduced Thrombosis Risk

In contrast to erythritol’s concerning effects on blood clot formation, Choi et al. (2024) found that allulose had a protective role in platelet function and cardiovascular health. Rather than promoting platelet aggregation, allulose actively suppressed platelet activation, reducing the likelihood of excessive clot formation. This is an important finding, as excessive platelet activation is a key contributor to thrombosis, which can lead to serious cardiovascular events such as strokes and heart attacks.

In the study, mice fed a high-fat, Western-style diet exhibited increased platelet aggregation, a condition that predisposes individuals to thrombotic complications. When erythritol was introduced, the effect worsened, but when allulose was introduced, the opposite effect was observed—platelet activation was suppressed, and pro-thrombotic pathways were downregulated. This suggests that allulose may counteract some of the clot-promoting effects of poor dietary habits and metabolic dysfunction.

Dr. Nick Norwitz, in his video analysis of these findings, emphasized the favorable metabolic properties of allulose, particularly its effects on reducing oxidative stress and enhancing mitochondrial efficiency. These findings are especially relevant for individuals at heightened risk of cardiovascular disease, including those with type 1 diabetes, where cardiovascular complications remain a leading cause of morbidity and mortality.

The study also explored the gene expression pathways involved in thrombosis and sickle cell disease (SCD). While erythritol mimicked the harmful pathways observed in SCD, allulose exhibited the opposite effect, downregulating those same pathways. This suggests that allulose could be particularly beneficial in individuals who are prone to clot formation, whether due to genetic factors (such as SCD), metabolic conditions (such as diabetes), or diet-induced cardiovascular risk factors.

Additionally, allulose was found to improve mitochondrial function, particularly in pathways related to ATP synthesis and oxidative stress mitigation. Mitochondrial dysfunction has been strongly linked to insulin resistance, inflammation, and cardiovascular disease. By enhancing mitochondrial efficiency, allulose appears to support overall metabolic health, making it an attractive alternative to other sugar substitutes that may carry more significant risks. Given these findings, allulose may be a metabolically favorable choice for individuals following a low-carb or therapeutic carbohydrate reduction diet. Not only does it provide a sweetening alternative with minimal impact on blood glucose, but it also appears to actively support cardiovascular health and metabolic function, distinguishing it from erythritol and other commonly used sugar alcohols.

2. Allulose and Mitochondrial Health

A key differentiator between erythritol and allulose lies in their respective effects on mitochondrial function. Choi et al. (2024) demonstrated that allulose had a positive impact on mitochondrial pathways, whereas erythritol downregulated critical genes involved in energy metabolism. Specifically, allulose upregulated genes associated with ATP production and electron transport chain function, which are vital for maintaining efficient cellular energy metabolism.

Mitochondria, often referred to as the “powerhouses” of the cell, are responsible for producing ATP, the body's primary energy currency. Dysfunction in mitochondrial pathways has been linked to various metabolic disorders, including insulin resistance and diabetes-related complications. In this study, allulose enhanced mitochondrial efficiency by supporting ATP synthesis and oxidative stress mitigation, potentially reducing the metabolic burden associated with diabetes and other chronic diseases.

These findings are particularly relevant for individuals managing diabetes and metabolic syndrome, as mitochondrial dysfunction is a well-established contributor to insulin resistance. When mitochondria are inefficient, cells struggle to process glucose effectively, leading to higher blood sugar levels and increased insulin demand. Over time, this metabolic instability contributes to worsening insulin resistance, systemic inflammation, and increased cardiovascular risk.

In contrast to erythritol, which was shown to impair mitochondrial function, allulose promoted cellular energy efficiency, which could translate into improved metabolic stability. By enhancing mitochondrial performance, allulose may help individuals with diabetes maintain better blood sugar control and reduce their long-term risk of diabetes-related complications.

Furthermore, Choi et al.'s study highlighted allulose’s potential in mitigating oxidative stress, a significant factor in mitochondrial dysfunction and cellular damage. Excess oxidative stress is a known driver of chronic inflammation, endothelial dysfunction, and cardiovascular disease—conditions that disproportionately affect individuals with type 1 diabetes. By reducing oxidative damage and enhancing ATP production, allulose supports cellular resilience, making it an attractive alternative to other sugar substitutes that may exacerbate metabolic stress.

These results align with Dr. Nick Norwitz’s analysis, where he emphasized that allulose consistently demonstrates beneficial effects on mitochondrial function. He pointed out that by improving ATP synthesis and reducing oxidative stress, allulose may offer metabolic advantages, particularly for those following low-carb or therapeutic carbohydrate reduction (TCR) diets.

Given its unique ability to support mitochondrial efficiency while minimizing oxidative stress, allulose emerges as a promising sugar alternative, particularly for individuals who need stable blood glucose control and want to minimize their long-term risk of metabolic complications.

3. Implications for Type 1 Diabetes Management

For individuals using therapeutic carbohydrate reduction (TCR) to manage type 1 diabetes, the choice of sugar substitute is more than just a matter of taste—it can have critical implications for both short-term blood glucose stability and long-term health outcomes. Recent research by Choi et al. (2024) suggests that erythritol may pose unexpected risks, particularly for individuals already predisposed to cardiovascular complications, whereas allulose appears to offer a more metabolically favorable alternative.

Erythritol’s Potential Risks in Type 1 Diabetes

One of the primary concerns regarding erythritol consumption is its association with increased blood clotting risk, as demonstrated in Choi et al.’s study. The research found that erythritol exacerbated platelet aggregation, which could contribute to thrombosis (blood clot formation) and cardiovascular disease progression. This is particularly troubling for individuals with type 1 diabetes, who already face a significantly heightened risk of cardiovascular complications.

The findings from Witkowski et al. (2023) further reinforce these concerns, as their study identified a strong correlation between erythritol levels and major adverse cardiovascular events (MACE), such as stroke and heart attack. The fact that erythritol not only correlates with but may actively promote clotting risk suggests that it may be an inappropriate sugar substitute for individuals managing type 1 diabetes, where cardiovascular health is a top concern. Additionally, Choi et al.’s research demonstrated that erythritol mirrored gene expression pathways observed in sickle cell disease (SCD)—a disorder known for its increased risk of blood clot formation. This raises further red flags about erythritol’s potential impact on vascular health, particularly in those who are already at risk for circulatory complications.

Allulose’s Potential Benefits for Type 1 Diabetes

In contrast, allulose demonstrated the opposite effects in Choi et al.’s study, showing potential advantages for individuals looking to maintain metabolic stability while following a TCR-based approach to diabetes management.

Allulose’s benefits stem from several key mechanisms:

1. Reduced Clotting Risk: Unlike erythritol, allulose actively suppressed platelet aggregation, reducing the likelihood of blood clot formation. This suggests that allulose may be a safer alternative for individuals at heightened cardiovascular risk—a major advantage for those managing type 1 diabetes, where preventing thrombosis is crucial.

2. Improved Mitochondrial Function: Allulose enhanced ATP production and upregulated electron transport chain pathways, which are key components of cellular energy metabolism. Given that mitochondrial dysfunction is a well-documented contributor to insulin resistance and metabolic instability, allulose’s ability to support mitochondrial health could have significant implications for diabetes management.

3. Low Glycemic Impact: Allulose is known for its minimal effect on blood glucose levels, making it a desirable sweetener for individuals following a low-carbohydrate diet to manage their type 1 diabetes. This is a critical factor, as maintaining stable blood glucose levels is one of the biggest challenges in diabetes management.

Practical Considerations for Individuals with Type 1 Diabetes

Given these findings, those with type 1 diabetes who use sugar substitutes should carefully evaluate their options. While erythritol has traditionally been considered a “safe” low-calorie sweetener, emerging evidence suggests that it may have unintended consequences that warrant caution, particularly for individuals already at high cardiovascular risk.

On the other hand, allulose presents a compelling alternative due to its potential cardiovascular benefits, mitochondrial support, and glycemic stability. As Dr. Nick Norwitz emphasized in his analysis, allulose has demonstrated a strong safety profile while actively promoting metabolic health—making it a more suitable choice for individuals managing type 1 diabetes through TCR.

Ultimately, while no sweetener is essential to a low-carb lifestyle, those who choose to use one should consider allulose as a potentially safer and more beneficial option compared to erythritol. Given the increased cardiovascular risks already present in type 1 diabetes, minimizing potential pro-thrombotic agents like erythritol could be an important step in optimizing both short-term glycemic control and long-term health outcomes.

Practical Considerations: Should You Switch to Allulose?

Given the latest research, individuals using erythritol may want to consider transitioning to allulose, particularly if they have underlying cardiovascular concerns. However, there are a few practical factors to keep in mind:

1. Availability and Cost
Allulose is still less widely available than erythritol and tends to be more expensive. While its price has been decreasing as demand increases, it remains a more premium option.

2. Tolerance and Digestive Effects
Both erythritol and allulose are well-tolerated in moderate amounts, but excessive consumption can cause digestive discomfort. Erythritol, in particular, is known for its laxative effect when consumed in large quantities. Allulose, while generally easier on the gut, may still cause bloating in sensitive individuals.

3. Future Research
While the current data is compelling, more long-term human trials are needed to confirm the cardiovascular effects of erythritol and allulose. Given the rapid pace of research in this field, individuals may want to stay informed about new findings that could further clarify the risks and benefits of these sugar substitutes.

Conclusion: The Future of Sweeteners in a Low-Carb Diet

The recent research on erythritol and allulose provides a strong case for reconsidering the role of sugar substitutes in metabolic health. While erythritol has been a staple in many low-carb and diabetes-friendly products, its potential role in promoting blood clotting and mitochondrial dysfunction raises serious concerns.

On the other hand, allulose appears to offer metabolic advantages, reducing thrombotic risk and improving mitochondrial efficiency. For those following a therapeutic carbohydrate reduction approach for type 1 diabetes, this could make allulose the better choice.

As research continues to evolve, the key takeaway is clear: not all sugar substitutes are created equal, and choosing the right one can have meaningful implications for long-term health.

Watch Dr. Norwitz’s video on this subject matter: https://www.youtube.com/watch?v=YZ9WLMS7ib4

Read Dr. Norwitz’s Substack: https://staycuriousmetabolism.substack.com/p/is-this-the-end-of-erythritol?r=40ekz2

Access the Latest Study: https://www.mdpi.com/2072-6643/16/24/4295