COGNITIVE:  New study links aspartame to learning and memory deficiencies…

By Robert Thomas

Ongoing work by Florida State University College of Medicine researchers into how aspartame affects the brain has linked the artificial sweetener with learning and memory deficits in mice.

The offspring of male mice that consumed aspartame at levels equivalent to much lower doses than those deemed safe by the US Food and Drug Administration (FDA), demonstrated spatial learning and memory deficits over the course of a controlled 16-week exposure. The study is published in Scientific Reports.

And while recent World Health Organization guidelines point out potential associations between the consumption of aspartame and other artificial sweeteners and increased risk for metabolic disease, cardiovascular disease and cancer, they did not address potential effects on cognitive abilities.

“This is a cognitive function that is distinct from the anxiety behaviour r, so the effects of aspartame are much more widespread than the previous paper had suggested,” said co-author Pradeep Bhide, the Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience in the Department of Biomedical Sciences.

The most recent research is an extension of the work the Bhide Lab produced in a study published in the Proceedings of the National Academy of Sciences in December 2022, which linked aspartame consumption to anxiety in mice, with effects extending up to two generations. “There is some overlap in terms of learning, memory and anxiety, in the sense that often there is an emotional component to our learning,” Bhide said. “When there’s an emotional impact, you remember better. But this is a quite distinct function and brain network.

“The second thing we noticed here, unlike the anxiety (research), this went only one generation. It was not seen in the grandchildren, only in the children [of the male mice], which is another line of support that these kinds of transmissions occur due to epigenetic changes in the sperm.”

Over the course of 16 weeks, the mouse models were separated into three groups: a control group that consumed only water, a group that ingested seven of the FDA’s recommended maximum intake of aspartame – equivalent to nearly 794mg (28 oz) diet sodas daily – in its water, and a group that ingested 15 percent aspartame 1 361mg (4 8 oz. diet sodas daily) in its water.

These are the same levels of aspartame exposure the Bhide Lab used in its anxiety research.

All of the mouse models were tested at four-, eight- and 12-week intervals in a Y-maze, and again at 12 weeks in a Barnes maze. In the latter, the mice learn to find a “safe” escape box out of 40 possible choices arranged in a circular arena.

The mice in the aspartame-free control group found the “safe” box quickly. Those that ingested aspartame took much longer to learn the task.

“We’re seeing they use a different strategy, but they do find the escape box,” said co-author Deirdre McCarthy, research faculty in the Department of Biomedical Sciences and the Centre for Brain Repair. “They compensate in some sort of way.”

The compensation to overcome learning and memory deficits is significant, according to Bhide.

“Again, they can function, but they need longer time, or may need extra help,” he said, suggesting that the FDA takes a closer, multi-generational perspective on the effects of aspartame.”

Additional co-researchers of the published study include Biomedical Sciences researcher Sara Jones, Associate Professor Gregg Stanwood and FSU Department of Psychology Professor Christopher Schatschneider.

‘CELL THERAPY CAN REDUCE RISK FROM COVID DEATH’

CLINICAL: Brazilian, German and United States researchers in a joint study conducted in 30 countries find that advanced cell therapy can limit the severity of the inflammatory response in COVID-19 patients…

By WSAM Correspondent

The use of cell therapy to treat COVID-19 patients can reduce the risk of death from the disease by 60 percent, according to a systematic review and analysis conducted by researchers at the University of São Paulo (USP) in Brazil, in partnership with colleagues in Germany and the United States.

Their findings are reported in an article published in the journal Frontiers in Immunology. The review covers 195 clinical trials of advanced cell therapies targeting COVID-19 that were conducted in 30 countries between January 2020 and December 2021, as well as 26 trials with outcomes published by July 2022. Cell therapy has come into increasingly frequent use in recent years to treat several diseases, especially cancer. It consists basically of introducing healthy cells into the patient’s organism in order to restore or alter certain sets of cells, carry a therapy through the body, or modulate the function of diseased cells.

The technique uses stem cells and derivatives from the patient (autologous) or from a donor (allogenic). The cells are cultured or modified in the laboratory before being administered. According to the article, the cell types most frequently used in clinical trials relating to treatment of COVID-19 in the period were multipotent mesenchymal stem (stromal) cells from connective tissue, used in 72% of the studies reviewed; natural killer cells from lymphoblasts, used in 9%; and mononuclear cells from blood, used in 6%.

“Cell therapy has advanced significantly in recent years and has been used to treat cancer and auto-immune, heart and infectious diseases. During the pandemic, it was used to treat COVID-19 in several clinical trials. Our study is the first to review all the information on these experiences scattered around the world and to verify by means of a meta-analysis [a statistical method of aggregating data from many independent studies] how cell therapy functions when used to treat COVID-19 and related complications,” said Otávio Cabral-Marques, a professor at USP’s Medical School and coordinator of the study.

Stem cell therapy and models involving organoids derived from stem cells drew a great deal of attention as novel methods for treating and studying COVID-19 during the pandemic, he noted, given the significant immune regulatory power and tissue repair functions of stem cells, especially the mesenchymal variety. In the case of the lungs, for example, clinical trials have shown to a greater or lesser extent that advanced cell therapy can limit the severity of the inflammatory response in COVID-19 patients, reduce pulmonary damage, improve lung function and help combat fibrosis.

Despite the attention paid to cell therapy, the real protection assured by vaccination should be stressed, according to Cabral-Marques. “Although all these studies have shown that advanced cell therapy could become established soon as an important adjunct treatment for these patients, prevention of the disease by vaccination remains the best protection,” he said.

The clinical trials involving advanced cell therapy for COVID-19 analysed by the authors of the review article were conducted in 30 countries, mainly the United States, China, Iran and Spain. They were highly heterogeneous, however, with widely varying numbers of participants, designs and methodologies, so for meta-analysis purposes the researchers created a specially curated COVID-19 trials database at CellTrials.org with several quality refinements, such as inclusion of trials from all national registries, exclusion of false positives on keywords, and exclusion of double counting of the same trials. The authors also note differences in terms of the phases of trials. In many countries, especially in Europe, strict regulation limits the number of human cell therapy products with established safety profiles that can be trialled, and 56% of the trials did not reach phase 2, which typically focuses on determining safety, efficacy and dose-response in a few hundred volunteers with the disease. Another limitation was that 31% of the trials analysed did not have a control group.

“To arrive at such a large reduction in the risk of death, we had to take into account the findings and characteristics of the different studies, as well as making a certain number of corrections and estimates,” said Igor Salerno Filgueiras, a PhD candidate and co-author of the article.

“There are techniques to standardize the data, eliminate biases and produce an impartial result, enabling analysts to reach conclusions that often go unnoticed in a specific study but add up to relevant scientific evidence when they are reinforced by other data,” said Dennyson Leandro M. Fonseca, another co-author and the recipient of a PhD scholarship from FAPESP.

Fabrication and clinical delivery methods in studies involving mesenchymal stem cells were “remarkably heterogeneous”, according to the article. “The results highlight the important role these cells can play in adjuvant therapies for COVID-19 and the associated complications. However, they also point to a need for better control of key parameters relating to the way the cell therapy products are made if we are to assure comparability between studies,” Cabral-Marques said.