Long-term study alludes to artificial sweeteners and cognitive decline link

By Nicola Gordon-Seymour

- Last updated on GMT


Related tags Cognitive decline Artificial sweeteners ISA

Results of a Spanish study appear to corroborate a link between artificial sweeteners and impaired metabolism and oxidative stress, which can exacerbate cognitive decline (CD).

Data collected over a 12-year period and validated in two separate sample sets may provide the most comprehensive characterisation of the human food metabolome in CD research to date.

“Accumulating evidence with animal models suggests that chronic intake of non-caloric artificial sweeteners may impair cognitive performance by causing dysregulation of the energy metabolism and oxidative stress,” ​the authors write.

However, this is, to our knowledge, the first time that this hypothesis linking artificial sweeteners with CD is corroborated from a long-term perspective, and also validated in two separate sample sets​.”

In response, The International Sweeteners Association (ISA) suggests the findings are misleading as they fail to provide evidence of a causal relationship between artificial sweeteners and CD. In addition, the results are arguable due to study limitations.

A spokesperson says: “This study shows only a borderline association between low/no calorie sweeteners intake at one point of time, in the beginning of the study, and the risk of developing cognitive decline 12 years later, without knowing if the participants continued to consume low/no calorie sweeteners, how much they consumed, or what other foods their diet included.

“In fact, several potential dietary or other confounding factors may have affected the observed association.”

Metabolites and CD

Lifestyle and diet are known factors in age-related CD and dementia, and nutrition is deemed pivotal in maintaining proper brain function with increasing age however most of the data is observational, inconsistent, and fragmented.

Therefore, a large-scale investigation of food-related metabolites was crucial to clarify the role of nutrition in the early pathogenesis of CD, the authors write.

The European study was conducted by a team at the University of Barcelona with a view to analysing the importance of diet on CD, from the context of gut microbiota and endogenous metabolism.

It focused on a large cohort of older subjects in France: 418 in Bordeaux (discovery) and 424 in Dijon (validation), who were free from dementia at baseline and split into two groups (case and control).

Cell metabolomics were analysed, including polyphenolic and other food-origin compounds, microbiota-transformed derivatives, and other metabolites, to assess the impact of specific food on metabolic reactions.

Positive and negative results

Results indicate specific metabolites play a pivotal role in the evolution of cognitive impairment and dementia.

For example, biomarkers for coffee and cocoa (2-furoylglycine and 3-methylanthine) had a protective function, while saccharin from artificial sweeteners and fatty acids had a damaging effect.

Ethyl sulphate, a biomarker for total alcohol intake, was also associated with increased odds of subsequent CD.

Conversely, the analysis suggested “a protective association of metabolites potentially reflecting red wine consumption​”.

An inverse association was observed between various phenolic acids and other plant-related metabolites derived from cocoa, coffee, mushrooms, and polyphenol-rich foods (such as apple, green tea, blueberries, oranges, or pomegranate), which provided evidence to support the protective effect of polyphenol-rich food on neurological function.

The scientists also observed a strongly correlation between citrus fruits and higher odds of subsequent CD, although this was attributed to consumption of commercial juices rather than the raw fruit - and contrary to a significant body of evidence on the benefits of citrus fruit consumption.

“Although not corroborated with food intake data (not available for the validation set), this is in line with previous studies reporting that the consumption of total citrus fruits is related to lower risk of dementia. Conversely, univariate statistics revealed a protective association of citrus markers with CD.”


The study offers a valuable insight into early metabolic events associated with the later risk of cognitive decline within the context of diet, gut microbiota and endogenous metabolism, and could help identify preventive and therapeutic strategies to preserve cognitive health.

The authors conclude that changes in lifestyle and diet are decisive as a strategy to prevent cognitive deterioration and its progression in neurodegenerative diseases, including Alzheimer’s.

They comment that a “higher intake of fruits, vegetables and plant-based foods provides polyphenols and other bioactive compounds … could help reduce the risk of cognitive decline due to ageing"​.

Source: Molecular Nutrition & Food Research

Published: 18 October 2021, https://doi.org/10.1002/mnfr.202100606

‘Food and Microbiota Metabolites Associate with Cognitive Decline in Older Subjects: A 12-Year Prospective Study’

Raúl González-Domínguez et al.

Related topics Research Cognitive function

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