The review, by scientists from the University of Pretoria and the University of Limpopo and published recently in the European Journal of Clinical Nutrition , indicated that high consumption of the sweetener may lead to neurodegeneration.
Aspartame is made up of phenylalanine (50 per cent), aspartic acid (40 per cent) and methanol (10 per cent).
It is commonly used in food products for the diet or low calorie market, including soft drinks and chewing gums.
It was approved for use in foods in the US and EU member states in the early 1980s.
The sweetener has caused much controversy amid suspicions on whether it is entirely safe, with studies linking the ingredient and cancer in rats.
It has also previously been found that aspartame consumption can cause neurological and behavioural disturbances in sensitive individuals.
Symptoms that have been reported include headaches, insomnia and seizures.
Despite strong concerns being raised from some quarters over the sweetener, both the European Food Safety Authority (EFSA) and the US Food and Drug Administration (FDA) have not changed their guidelines regarding the safety of the ingredient or intake advice.
The new review also challenges finding published last year in the journal Critical Reviews in Toxicology (Informa Healthcase) that considered over 500 studies, articles and reports conducted over the last 25 years - including work that was not published, but that was submitted to government bodies as part of the regulatory approvals process.
The earlier review concluded: "The weight of existing evidence s that aspartame is safe at current levels of consumption… No credible evidence was found that aspartame is carcinogenic, neurotoxic, or has any other adverse effect on health when consumed even at quantities many times the established ADI [acceptable daily intake] levels."
New review Writing in the European Journal of Clinical Nutrition , a Nature journal, the scientists behind the new review state: "The aim of this study was to discuss the direct and indirect cellular effects of aspartame on the brain, and we propose that excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders, and also in compromised learning and emotional functioning."
The researchers found a number of direct and indirect changes that occur in the brain as a result of high consumption levels of aspartame, leading to neurodegeneration.
They found aspartame can disturb the metabolism of amino acids, protein structure and metabolism, the integrity of nucleic acids, neuronal function and endocrine balances.
It also may change the brain concentrations of catecholamines, which include norepinephrine, epinephrine and domapine.
Additionally, they said the breakdown of aspartame causes nerves to fire excessively, which can indirectly lead to a high rate of neuron depolarisation.
The researchers added: "The energy systems for certain required enzyme reactions become compromised, thus indirectly leading to the inability of enzymes to function optimally.
"The ATP stores [adenosine triphosphate] in the cells are depleted, indicating that low concentrations of glucose are present in the cells, and this in turn will indirectly decrease the synthesis of acetylcholine, glutamate and GABA (gamma-aminobutyric acid)."
Furthermore, the functioning of glutamate as an excitatory neurotransmitter is inhibited as a result of the intracellular calcium uptake being altered, and mitochondria are damaged, which the researchers said could lead to apoptosis (cell death) of cells and also a decreased rate of oxidative metabolism.
As a result of their study, the researchers said more testing is required to further determine the health effects on aspartame and bring an end to the controversy.
Source: European Journal of Clinical Nutrition 2008, doi: 10.1038/sj.ejcn.1602866
"Direct and indirect cellular effects of aspartame on the brain" Authors: P. Humphries, E. Pretorius, H. Naude