What are the long term side effects of artificial sweeteners?

October 24, 2025 •

4 min read

Observational studies have found an association between long-term consumption of artificial sweeteners and an increased risk of cardiovascular disease. Understanding the full scope of what are the long term side effects of artificial sweeteners is crucial for making informed dietary choices.

Quick Summary

Long-term consumption of artificial sweeteners is associated with potential risks to metabolic function, gut microbiome balance, and cardiovascular health. These sugar substitutes, including aspartame and sucralose, have been linked to insulin resistance, altered glucose metabolism, and increased risk of heart-related issues, contrary to their reputation as harmless alternatives.

Key Points

Metabolic Disruption: Long-term use of artificial sweeteners like sucralose may contribute to insulin resistance and altered glucose metabolism, ironically affecting metabolic health.
Cardiovascular Risks: High consumption of certain artificial sweeteners, including aspartame, sucralose, and acesulfame potassium, has been linked to an increased risk of cardiovascular disease, stroke, and heart attack.
Gut Microbiome Alterations: Sweeteners such as saccharin and sucralose can alter the balance of gut bacteria, potentially leading to dysbiosis, inflammation, and downstream health issues.
Potential Neurological Effects: Aspartame has been associated in some studies with mood disorders, headaches, and concerns about long-term neurodegeneration, though evidence is controversial and requires more research.
Conflicting Evidence: While some regulatory bodies deem artificial sweeteners safe at moderate levels, scientific studies present conflicting results, emphasizing the need for more high-quality, long-term human research.
Consideration of Moderation: The safest approach is to limit overall sweetener consumption, artificial or otherwise, and prioritize a whole-foods diet for better long-term health outcomes.

The Controversy Surrounding Artificial Sweeteners

Artificial sweeteners, also known as non-nutritive sweeteners (NNS), are widely used as sugar substitutes in thousands of food and beverage products. They offer sweetness without the calories, making them popular for weight management and blood sugar control. However, accumulating scientific evidence suggests that long-term, high-dose consumption may have adverse health effects, challenging their perceived benefits. Concerns exist about how these compounds interact with the body, potentially disrupting gut bacteria and affecting metabolic and cardiovascular systems.

How Artificial Sweeteners May Impact Metabolic Health

Many choose artificial sweeteners to avoid metabolic issues linked to sugar, but research suggests NNS might contribute to metabolic dysregulation long-term.

Insulin Resistance: Chronic sucralose use may lead to insulin resistance, a precursor to type 2 diabetes. While there might be an initial increase in insulin secretion, long-term exposure could reduce this response.
Altered Glucose Metabolism: Some NNS can alter glucose tolerance and glycemic responses, even below acceptable daily intake levels. This effect is often linked to changes in the gut microbiome.
Paradoxical Weight Gain: Despite being calorie-free, diet sodas and other products with artificial sweeteners have been linked to weight gain and metabolic syndrome in some observational studies. This might disrupt hunger and satiety regulation, potentially increasing cravings for high-calorie foods.

The Connection to Cardiovascular Disease

The link between artificial sweeteners and cardiovascular health is a significant concern, with several large studies indicating potential risks.

Increased Risk of CVD Events: A large study in The BMJ found a potential link between higher NNS intake and increased risk of overall cardiovascular diseases, including coronary heart disease and stroke. Aspartame, acesulfame potassium, and sucralose were specifically highlighted.
Role of Erythritol: A study in Nature Medicine associated higher blood levels of erythritol with an increased risk of heart attack and stroke. Lab tests suggested erythritol could promote blood clot formation.
Systemic Inflammation: NNS-induced changes in the gut microbiome can increase intestinal permeability, leading to systemic inflammation, a known risk factor for cardiovascular issues.

Disruptions to the Gut Microbiome

The gut microbiome is crucial for metabolic function and health. Artificial sweeteners can significantly alter this microbial community.

Altered Bacterial Composition: Studies on sweeteners like saccharin and sucralose show disruption in beneficial gut bacteria. Some research points to a decrease in beneficial bacteria and an increase in potentially harmful strains.
Impaired Glucose Regulation: Changes in gut bacteria are linked to impaired glucose tolerance in studies. Restoring gut microbiome balance can normalize glucose metabolism.
Increased Toxin Pathways: A study on aspartame found it could enrich bacterial pathways linked to cylindrospermopsin, a toxin potentially harmful to the liver and nervous system.

Potential Neurological Effects

Concerns exist about the potential long-term neurological impact of certain artificial sweeteners, particularly aspartame, although evidence is often inconclusive.

Headaches and Depression: Aspartame has been linked to headaches, mood disorders, and depression in some studies and anecdotal reports. Its breakdown products can affect neurotransmitter levels.
Neurodegeneration: A 2021 review suggested a potential link between long-term aspartame use and increased risk of neurodegenerative disorders, though this is controversial. A metabolite can produce formaldehyde, which may cause oxidative damage to brain cells.
Elevated Stress Response: Aspartame may act as a chemical stressor, increasing cortisol levels and potentially making the brain more vulnerable to oxidative stress.

Weighing the Risks: A Comparison of Common Artificial Sweeteners


Artificial Sweetener	Long-Term Metabolic Concerns	Long-Term Cardiovascular Concerns	Long-Term Gut Health Concerns	Other Potential Risks
Aspartame	Potential link to insulin resistance and altered glucose metabolism in some studies.	Associated with increased risk of cerebrovascular events in high consumers.	Altered gut microbiome, potentially enriched toxin pathways.	Headaches, mood disorders, and neurodegenerative risks suggested in some reviews, though controversial.
Sucralose (Splenda)	May lead to insulin resistance and altered glucose and lipid metabolism.	Associated with increased coronary heart disease risk.	Disrupts gut bacteria balance, reduces beneficial bacteria.	Heating can produce potentially toxic compounds.
Saccharin (Sweet'N Low)	Linked to glucose intolerance and metabolic disease risk through gut alterations.	Association with increased risk of metabolic syndrome and related cardiometabolic issues.	Alters gut microbiota, potentially increases certain bacteria types.	Concerns regarding bladder cancer in rats were not found to apply to humans; requires high doses for any potential risk.
Acesulfame Potassium (Ace-K)	May alter energy metabolism and impact body weight in animal studies.	Associated with increased coronary heart disease risk.	Potential to affect gut bacteria, especially in mice.	Genotoxic effects and potential for weight gain in male mice models.
Erythritol	Potential for adverse cardiovascular events in individuals with pre-existing risks.	Linked to increased risk of heart attack and stroke due to heightened blood clot formation.	May cause digestive issues like bloating and gas.	Potential long-term health risks not yet fully understood due to limited research.

What the Regulatory Bodies and Researchers Say

While some agencies consider artificial sweeteners safe within acceptable daily intakes (ADIs), the scientific community is divided. The IARC classified aspartame as "possibly carcinogenic to humans" in 2023, based on limited evidence. However, JECFA maintained that the ADI for aspartame was safe. The debate and conflicting results from studies highlight the need for more high-quality, long-term human research. Health organizations often recommend focusing on a healthy, whole-foods diet instead of relying on NNS for weight control.

Conclusion: Navigating a Sweet but Controversial Topic

While artificial sweeteners are calorie-free sugar alternatives, evidence for potential long term side effects of artificial sweeteners is growing. Risks concerning metabolic dysfunction, cardiovascular health, gut microbiome disruption, and neurological issues have been suggested in numerous studies, though causality is still being investigated. Effects can vary by sweetener and individual factors, and other lifestyle choices may influence some observed associations. Reducing reliance on sweeteners and prioritizing a balanced, whole-foods diet is generally the safest approach for long-term health. Consulting a healthcare professional for personalized dietary advice is recommended.

For more information on sweeteners and health, consult resources like the Mayo Clinic.

Frequently Asked Questions

Current evidence suggests there is no strong link between artificial sweeteners and cancer in humans at typical consumption levels. Concerns arose from animal studies in the 1970s involving high doses of saccharin, but these findings do not apply to people. While the IARC classified aspartame as 'possibly carcinogenic' in 2023, the classification was based on limited evidence.

Paradoxically, some long-term observational studies suggest an association between artificial sweetener consumption and weight gain, contradicting their intended use for weight management. This may be because they disrupt hunger and satiety signals or increase cravings for sweet foods, though confounding factors exist.

Artificial sweeteners can disrupt the balance of the gut microbiome, a condition known as dysbiosis. Studies have shown that sweeteners like saccharin and sucralose can alter the composition of gut bacteria, which can lead to metabolic disturbances and inflammation.

The safety of artificial sweeteners is still a subject of ongoing debate and research, with varying levels of evidence regarding their long-term effects. While specific issues have been raised for different sweeteners (e.g., erythritol and heart health, aspartame and neurological effects), it's difficult to label one as definitively safer than another. Moderation and a balanced diet are recommended over reliance on any single sweetener.

Yes, some studies indicate that long-term consumption of certain artificial sweeteners, such as sucralose, can lead to insulin resistance and altered glucose metabolism, potentially impairing the body's ability to regulate blood sugar. These effects appear to be mediated, at least in part, by changes to the gut microbiome.

This depends on individual health goals and medical conditions. For those needing to control blood sugar, artificial sweeteners offer a zero-calorie option. However, the long-term risks associated with artificial sweeteners suggest that consuming them in moderation is prudent. The best strategy for most people is to reduce overall intake of sweet products, both with sugar and artificial sweeteners, and focus on whole, unprocessed foods.

Common digestive side effects, particularly when consumed in large amounts, can include bloating, gas, stomach cramps, and diarrhea. Some sweeteners, especially sugar alcohols, are known to cause these issues more frequently.