I have several concerns about this study. The authors claim that the consumption of Aspartame by adults and children "often exceeds those levels recommended by the FDA". This is extremely unlikely in my view. The FDA-acceptable daily intake of Aspartame is 50 mg per kg of body weight per day. I weigh 80 kg, so this means this means the FDA-based safe dose for me is 4000 mg (or 4 grams) of Aspartame per day, every day, for life. Given a diet drink contains about 200 mg of Aspartame, I would have to drink the equivalent of 20 cans of diet soda a day to get this dose. A child of 40 kg would have to drink 10 cans a day, every day. Even then, the 50 mg/kg dose has a safety factor of 100 built-in. 

The study design also has some issues. The main one is that the authors used a particular type of lab mouse called an ApoE mouse, which is bred to be prone to heart disease. They also fed it a high-fat, high-cholesterol diet, which itself increases the risk of heart disease. They also don’t seem to have measured how much of the Aspartame water the mice drank, or the Aspartame level in the blood, so it is unknown what the mice actually received. 

To my mind, the author's admission that feeding mice that are already genetically susceptible to heart disease with a high-fat, high-cholesterol diet that is known to cause heart disease "diminishes clinical relevance" is somewhat of an understatement. We certainly can’t extrapolate these results to humans.

Contrary to the paper's claims, it is quite well-established that Aspartame doesn't stimulate glucose or insulin levels in humans.

Aspartame is, essentially, just two common amino acids (aspartic acid and phenylalanine) joined together. In the gut, it is broken down to aspartic acid and phenylalanine. There is no reason to think amino acids from Aspartame would be worse than those from any other source. 

The authors would appear to think little work has been done on safety testing in Aspartame; this is just not true. All food ingredients are rigorously tested and safety assessed before they are approved for use. Aspartame is one of the most researched ingredients in the world. It is just that a lot of the data is in safety assessments for regulatory approval, not the academic literature. 

Finally, even if Aspartame did cause some increase in cardiovascular risk (which this study does not prove), then that risk would likely be very small compared to things like high fat/high sugar diets and lack of exercise, etc.

In short, I don’t think you have to give up your diet Coke just yet.

This is yet another study that must be evaluated by food safety authorities within the framework of scientific evidence - in our case, as an EU country, by the European Food Safety Authority (EFSA). So far, like other food safety authorities worldwide and the FAO-WHO joint committee responsible for evaluating additives, [the EFSA] considers aspartame safe within the Acceptable Daily Intake limits. In the case of the European Union, this limit is set at a maximum of 40 mg/kg body weight per person per day, under the approved conditions for certain food products. Moreover, in 2013, EFSA conducted a re-evaluation of aspartame's approval, deeming it safe, and following the WHO's position in 2023, all food safety agencies worldwide continue to uphold the same approvals and conditions for aspartame. 

As the authors themselves indicate, there is a limitation in the study: the mouse or animal model may not be relevant to humans. This limitation is similar to many studies due to physiological aspects and the adaptation of metabolic processes in humans when ingesting certain nutrients or compounds. Aspartame is composed of L-aspartic acid and L-phenylalanine (two amino acids found in much larger amounts in many foods and beverages, such as milk). Aspartic acid is a non-essential amino acid that the human body can synthesize from other amino acids, while phenylalanine is one of the eight essential amino acids that the human body cannot produce and must obtain from food. It also contains a methyl group. During digestion in humans, hydrolysis occurs in the upper part of the duodenum, breaking down aspartame. This releases the two amino acids and forms methanol (ripe fruit and legumes also contain small amounts of methanol and substances that convert into methanol during digestion), which are absorbed and enter the bloodstream. The authors themselves highlight these dietary and compound-related aspects as a limitation. 

It is essential to conduct studies in humans and place trust in food safety authorities, just as active ingredients and medications are approved by regulatory agencies. Additionally, in the EU, the approval of any additive must later be authorized by the European Commission and published in the Official Journal of the European Union. Furthermore, under Regulation 178/2002, the EC can apply the precautionary principle, which, in specific circumstances—after assessing all available information and if there is a potential risk to health and scientific uncertainty—allows for the adoption of provisional risk management measures to ensure the high level of health protection upheld by the EC, including revoking authorization. When justified, certain additives have had their authorization removed. So far, in the case of aspartame, this has never happened. 

I believe the title of the paper should be: ‘Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation in mice.’ It is unclear why they excluded the fact that the study was conducted on mice from the title and only mentioned it as a limitation at the end of the paper.