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Dietary DHA prevents cognitive impairment and inflammatory gene expression in aged male rats fed a diet enriched with refined carbohydrates

Butler M, Deems N, Muscat S, Butt C, Belury M, Barrientos R (2021) Brain, Behaviour and Immunity Nov;98:198-209 doi: 10.1016/j.bbi.2021.08.214 

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The consumption of a processed foods diet (PD) enriched with refined carbohydrates, saturated fats, and lack of fiber has increased in recent decades and likely contributed to increased incidence of chronic disease and weight gain in humans.

These diets have also been shown to negatively impact brain health and cognitive function in rodents, non-human primates, and humans, potentially through neuroimmune-related mechanisms. However, mechanisms by which PD impacts the aged brain are unknown.

This gap in knowledge is critical, considering the aged brain has a heightened state of baseline inflammation, making it more susceptible to secondary challenges.

Here, we showed that consumption of a PD, enriched with refined carbohydrate sources, for 28 days impaired hippocampal- and amygdalar-dependent memory function in aged (24 months), but not young (3 months) F344 × BN rats.

These memory deficits were accompanied by increased expression of inflammatory genes, such as IL-1β, CD11b, MHC class II, CD86, NLRP3, and complement component 3, in the hippocampus and amygdala of aged rats.

Importantly, we also showed that when the same PD is supplemented with the omega-3 polyunsaturated fatty acid DHA, these memory deficits and inflammatory gene expression changes were ameliorated in aged rats, thus providing the first evidence that DHA supplementation can protect against memory deficits and inflammatory gene expression in aged rats fed a processed foods diet.

Lastly, we showed that while PD consumption increased weight gain in both young and aged rats, this effect was exaggerated in aged rats. Aging was also associated with significant alterations in hypothalamic gene expression, with no impact by DHA on weight gain or hypothalamic gene expression.

Together, our data provide novel insights regarding diet-brain interactions by showing that PD consumption impairs cognitive function likely through a neuroimmune mechanism and that dietary DHA can ameliorate this phenomenon.


Eating a diet rich in processed foods for just 4 weeks led to significant impairments in memory and cognition in ageing rats (but not in young animals) along with increased measures of inflammation in brain regions known to be critical for memory and learning.

Importantly, however, when the same diet was supplemented with the long-chain omega-3 fatty acid DHA (found in fish and seafood), this protected against both the memory and learning problems, and the neuroinflammation, caused by the processed food diet.

Similar pioneering research almost 10 years ago first showed that adding omega-3 fatty acids to the diet could protect against memory problems, brain changes and metabolic problems that were caused by only 6 weeks of high-sugar intake.

These findings reinforce those of many other studies showing that highly processed diets - high in sugar and refnied carbohydrates and lacking in omega-3 fatty acids - can rapidly cause memory and learning difficulties.    

Very importantly, they also support previous research showing that adding long-chain omega-3 fatty acids to such diets can protect against many of their damaging effects.  

For the related news article please see:

See also:

For a full list of research articles on the subject of 'ultra-processed' foods and their effects, please see:

And for more information on omega-3 fatty acids and the ageing brain, see: