
Aspartame has been used as a sweetener for decades and is found in everything from sugar-free soft drinks to chewing gum and desserts. For many people, it has become a regular alternative to sugar—especially in products marketed for weight management or reduced calorie intake. At the same time, aspartame has long been the subject of scientific debate, with ongoing research into questions of metabolism, blood sugar regulation, and potential long-term health effects.
In this blog, we take a closer look at new research that aims to explain how aspartame may influence the body at a molecular level—and why that could matter for cardiovascular health.
table of contents
What is aspertame?
Before getting started, it is useful to take a closer look at what aspartame actually is and why it is so widely used.
Aspartame is a low-calorie, high-intensity artificial sweetener that is around 200 times sweeter than sugar, which is why only small amounts are needed. In its pure form, it is a white, odourless powder.
In Europe, aspartame is authorised as a food additive and must be listed on labels either by name or by its E-number, E 951. It is commonly used in sugar-free soft drinks, chewing gum, light yoghurt and desserts, sugar-free sweets, and table-top sweeteners—often to help reduce sugar and calorie content.
Aspartame has been permitted for many years following safety assessments, and it was fully re-evaluated by the European Food Safety Authority in 2013.
Did you know?
Aspartame is a synthetic, high-intensity sweetener — whereas stevia is a naturally derived high-intensity sweetener.
Aspartame in recent research
Interest in aspartame has increased again following new research shared publicly by Harvard professor and longevity researcher Dr. David Sinclair. In a post on X, he highlighted a newly published study suggesting that aspartame may interact with biological pathways linked to type 2 diabetes and cardiovascular disease.
The study is based on computer modelling rather than experiments in living organisms. Using simulations, the authors propose a strong and stable binding between aspartame and PGC-1α, a regulator involved in muscle function, inflammation, and insulin sensitivity. The researchers describe these findings as hypotheses that need to be tested further in laboratory and human studies.
PGC-1α explained
PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a protein that plays a central role in energy metabolism. It helps regulate how mitochondria produce energy and is involved in muscle performance, endurance, inflammation, and insulin sensitivity. Because of its broad role in metabolic health, it is frequently studied in longevity and cardiometabolic research.
What do the key studies show?
To place the new modelling study in context, Sinclair also referenced two earlier publications.
One is a mechanistic study published in Cell Metabolism in 2025. This study explored how aspartame intake may influence hormonal and inflammatory pathways in experimental models. The researchers describe a sequence in which aspartame intake affects sweet-taste–related signalling, increases insulin release, and leads to changes in the blood vessel lining. A signalling molecule called CX3CL1 plays a central role in this process by attracting immune cells to the vessel wall. When this pathway was disrupted in the model, the observed effect on plaque development was no longer present.
These findings come from animal models and cannot be directly applied to humans. They do, however, suggest biologically plausible mechanisms that may be relevant for further research.
The second study is a large observational human study published in The BMJ in 2022, based on data from the French NutriNet-Santé cohort. More than 100,000 adults repeatedly reported their dietary intake, allowing researchers to estimate consumption of artificial sweeteners over time. Higher intake of artificial sweeteners overall was associated with a higher risk of cardiovascular disease. The analyses also looked at specific sweeteners, including aspartame, and found that associations varied depending on the outcome.
As with all observational studies, these findings cannot establish cause and effect. Lifestyle factors, underlying health status, and the reasons people choose sweeteners in the first place may influence the results.
CX3CL1 explained
CX3CL1 is a signalling molecule produced by cells in the blood vessel wall. It helps attract immune cells and can contribute to local inflammation.f inflammation and allergies.
What do public authorities say about artificial sweeteners and aspartame?
Based on the findings discussed above—and the way “sugar-free” products are often presented to consumers—it can be useful to step back and look at what international health authorities actually say about aspartame and non-sugar sweeteners more broadly. EFSA’s communication in Europe focuses on safety within a defined intake level, while WHO’s 2023 guidance focuses on whether non-sugar sweeteners should be used as a public health strategy for weight control and long-term health outcomes.
European Food Safety Authority — EFSA
EFSA’s assessment focuses on safety. Aspartame is considered safe for the general population when consumed within the established acceptable daily intake (ADI), which is set at 40 mg per kg of body weight per day. This conclusion was reaffirmed after EFSA’s full re-evaluation of aspartame in 2013.
World Health Organization —WHO
WHO approaches the topic from a public health perspective. In 2023, WHO issued a new guideline advising against using non-sugar sweeteners as a strategy for weight control or for reducing the risk of diet-related noncommunicable diseases. The guideline was based on a systematic review commissioned by WHO, which examined evidence from both randomized trials and observational studies. The conclusion was that the overall evidence does not show a clear long-term benefit for weight or health outcomes.
Why are artificial sweeteners still discussed?
Artificial sweeteners are often marketed as a healthier alternative to sugar, especially in products labelled “sugar-free” or “zero”. Today, they are also found in a wide range of everyday supermarket items—meaning they can become part of the regular diet for both adults and children. At the same time, public authorities communicate from different angles: EFSA focuses on safety within a defined intake limit, and that limit is set high enough that it can roughly correspond to as many as 15–20 cans of diet soda per day for an average adult depending on the product and body weight. WHO, on the other hand, evaluates whether using non-sugar sweeteners makes sense from a long-term public health perspective. When new experimental and observational studies are added to the picture—and when profiles such as David Sinclair bring those findings into the public conversation—it becomes easier to understand why the topic continues to raise questions and spark debate in health and longevity circles.
What does EFSA’s limit equal in practice?
EFSA’s acceptable daily intake (ADI) for aspartame is 40 mg per kg of body weight per day.
For an adult weighing around 70 kg, this equals roughly 2,800 mg per day.
A standard 330 ml can of diet soda typically contains about 120–180 mg of aspartame depending on the product.
In practical terms, EFSA’s ADI corresponds to approximately 15–20 cans of diet soda per day.
A more nuanced perspective going forward
Overall, the picture is still evolving. EFSA considers aspartame safe within the current intake limits, while WHO’s 2023 guideline takes a more cautious view on the use of artificial sweeteners as a tool for long-term weight control and overall health. At the same time, newer mechanistic studies, often based on animal models, along with large observational studies in humans, continue to add nuance and raise questions that go beyond calorie content alone.
At this point, the most reasonable takeaway is that the discussion around aspartame is rarely a simple yes-or-no issue. It is more about context and use: how often it appears in the diet, in which products, and what regular consumption may mean over time. Future research, particularly well-designed human studies, will be essential to clarify whether current recommendations remain appropriate or should be refined as the evidence base grows.
References
- European Food Safety Authority (EFSA).
Aspartame. EFSA; last reviewed 28 Jun 2023. Available from: https://www.efsa.europa.eu - .Xia M, Liu X, Wang K, Liang B, Xiao P.
From sweetener to risk factor: Network toxicology, molecular docking and molecular dynamics reveal the mechanism of aspartame in promoting coronary heart disease. Chem Biol Interact. 2026;424:111876. doi:10.1016/j.cbi.2025.111876 - Sinclair D. New paper: Aspartame, a synthetic dipeptide 200X sweeter than sugar, is linked to heart disease and Type 2 diabetes [Internet]. X (formerly Twitter); 15 Dec 2025 [cited 2025 Dec 15]. Available from: https://x.com/davidasinclair/status/2000582793051443630
- Wu W, Sui W, Chen S, Guo Z, Jing X, Wang X, et al.
Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. Cell Metab. 2025;37(5):1075–1088.e7. doi:10.1016/j.cmet.2025.01.006 - Debras C, Chazelas E, Sellem L, Porcher R, Druesne-Pecollo N, Esseddik Y, et al.
Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. BMJ. 2022;378:e071204. doi:10.1136/bmj-2022-071204 - EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS).
Scientific opinion on the re-evaluation of aspartame (E 951) as a food additive. EFSA J. 2013;11(12):3496. doi:10.2903/j.efsa.2013.3496 - World Health Organization (WHO). WHO advises not to use non-sugar sweeteners for weight control in newly released guideline [Internet]. Geneva: WHO; 15 May 2023 [cited 2025]. Available from: https://www.who.int
- World Health Organization (WHO). Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. Geneva: World Health Organization; 2022. ISBN: 978-92-4-004642-9

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