Brain & Neurons

Omega-3 Improves Memory Deficits From Processed Diet

Rats fed a processed diet high in refined carbohydrates have memory problems, which can be prevented by supplementing with an omega-3 called DHA.

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By Dylan G. Arrazati


  • Aged rats that consume a diet high in processed foods for 28 days exhibit cognitive deficits in brain regions linked to memory. 
  • Proinflammatory genes display greater activation in aged rats fed a processed diet. 
  • DHA mitigates memory impairments and lowers proinflammatory gene expression in aged rats fed a processed diet. 

In grocery stores and mini-marts all over the US, people are welcomed with walls and shelves lined with tantalizing processed foods rather than healthy fresh produce. Although your heart may desire that sweet soda or salty bag of chips, consuming processed foods contributes to poor overall health and aging. While studies have documented the harmful effects of a processed foods diet on brain health and cognitive function, we don’t fully understand how these impairments occur in aged brains. 

Butler and colleagues from Ohio State University published an article in Brain Behavior and Immunity showing that replenishing an essential omega-3 fatty acid called docosahexaenoic acid (DHA) attenuated memory impairments in aged rats on processed diets high in refined carbohydrates. In addition, the investigators demonstrated that DHA supplementation in aged rats mitigated processed diet-induced upregulation of genes that drive inflammation (proinflammatory) in brain regions linked to memory — hippocampus and amygdala. 

“These findings indicate that consumption of a processed diet can produce significant and abrupt memory deficits — and in the aging population, rapid memory decline has a greater likelihood of progressing into neurodegenerative diseases such as Alzheimer’s disease. By being aware of this, maybe we can limit processed foods in our diets and increase consumption of foods that are rich in the omega-3 fatty acid DHA to either prevent or slow that progression,” Senior study author Ruth Barrientos, an investigator in The Ohio State University Institute for Behavioral Medicine Research and associate professor of psychiatry and behavioral health.

What Are Refined Carbohydrates? 

When a substance is refined, it implies that certain elements or impurities have been eliminated, ideally resulting in a more pure product. Essentially, refined carbohydrates are energy molecules that have undergone extensive processing and refinement, but what’s left are carbohydrates that no longer carry the vital nutrients and minerals that our cells need to function properly. Studies also show that refined carbohydrates fail to provide long-lasting energy due to digestive enzymes breaking down these compounds much more quickly than regular carbohydrates. As many of our favorite processed foods contain refined carbohydrates, we must be aware of overconsumption’s possible metabolic and cognitive consequences. 

Why Is DHA Important?  

DHA is a vital unsaturated fatty acid predominantly found in fish and fish-oil supplements with various health benefits ranging from proper fetal development to protection against cardiovascular diseases. Other studies have linked DHA deficiency to elevated inflammation and neurodegeneration, putting aged individuals at higher risk due to DHA naturally declining with age. As aged humans present greater levels of inflammation in the nervous system (neuroinflammation) and diminished cognitive function, Butler and colleagues wanted to see if DHA supplementation could mitigate these types of effects that result from dietary injury.  

A Processed Foods Diet Impacts the Brain’s Response to Fear

Before experimentation, Butler and colleagues fed rats the following three diets for 28 days: Standard Chow Diet (32% protein, 54% complex carbohydrates, 14% fat), Processed Foods Diet (19.6% protein, 63.3% refined carbohydrates, 17.1% fat), and Processed Foods Diet plus DHA. They wanted to determine the impacts of processed foods on brain function and see if DHA supplementation affected those responses.

To do so, they performed experiments that examined the brains’ response to fear. Specifically, they looked at how different diets affected conditioned fear responses that rely on two brain regions, the hippocampus or amygdala. Whereas the amygdala stores the memories of stimulus-related to fear, the hippocampus contextualizes fear, tying fearful memories to where they happened.

To evaluate how diet affects hippocampal evaluation, Butler and colleagues placed rats on different diets in a conditioning chamber and, after a couple of minutes, played a tone. But this tone was paired with a footshock; every time the tone played, the rats received a shock. The thinking here is that the hippocampus would learn that the foot shock was tied to the tone. After hanging out for four days and eating their assigned diets, the rats were reintroduced into this conditioning chamber. Butler and colleagues observed that aged rats on a processed diet exhibited a lower contextual-fear response, indicating less hippocampal activity. What’s more, DHA supplementation ameliorated the diminished fear response in aged rats, showing that replenishing DHA levels in the brain can restore memory deficits induced by dietary injury. 

To examine amygdalar-dependent fear responses, the Ohio State University investigators used the same experiment except that, instead of placing the rats back into the same environment where they learned to link the shock to the tone, they put them in a new environment (or context) but played the same tone. They wanted to see if the rats still responded to the sound with fear in anticipation of a footshock in this novel context.

Butler and colleagues saw that aged rats demonstrated significantly lower fear behavior following tone activation, suggesting decreased amygdala activity. While a processed diet negatively affected hippocampal- and amygdalar-dependent responses in aged rats, young rats on a processed diet displayed similar responses to aged and young rats fed a standard chow diet. Thus, these findings demonstrate that aged brains are more susceptible to cognitive impairment, which likely can be attributed to higher baseline inflammation in aged brains. 

(Butler et al., 2021 | Brain, Behavior, and Immunity) Processed diet hampers contextual memory and cued-fear memory response in aged rats. These graphs show how diets — standard chow (chow), processed foods (PD), and processed foods plus DHA (PD + DHA) — affect the amount of freezing behavior in young (white bars) and aged (blue bars) rats during the contextual (left plot) and cued-fear (right plot) memory tests. 

Proinflammatory Genes Show Upregulation in Rats Fed a Processed Foods Diet 

After seeing the memory impairments in the hippocampus and amygdala, the research team looked at how gene activity changed in these brain parts. Analysis revealed that rats on a processed diet displayed increased levels of various proinflammatory genes, one being IL-1B. However, IL-1B levels in the hippocampus and amygdala decreased in rats fed a processed diet supplemented with DHA. Given that upregulation of IL-1B in the hippocampus has been linked to diminished learning capabilities and impaired memory, these findings suggest that DHA supplementation may be sufficient to ameliorate neuroinflammation that triggers these deficits upon dietary injury. 

Butler and colleagues also noticed that aged rats on a processed diet showed upregulation of the complement C3 gene, whose role contributes to the body’s innate immune response and memory formation. Notably, studies have shown that humans with Alzheimer’s disease exhibit increased C3 levels. That can happen, in part, due to the elimination of synapses, a neuronal junction that allows electrical or chemical signals to be transmitted between neurons. 

Upon DHA supplementation, aged rats showed significantly lower levels of C3 in the hippocampus and amygdala. Moreover, Butler and colleagues are the first to demonstrate that DHA supplementation can attenuate elevated C3 levels following dietary injury from processed foods. However, more research is needed to pinpoint the cellular mechanisms that trigger neuroinflammation and reduced cognition after consuming processed foods. 

(Butler et al., 2021 | Brain, Behavior, and Immunity) Processed diet induces upregulation of proinflammatory genes in the hippocampus and amygdala.  Proinflammatory gene levels in young (white bars) and aged (blue bars) rats following consumption of a standard chow diet (chow), processed diet (PD), or processed diet plus DHA (PD + DHA). These plots show the expression levels of IL-1B (top) and C3 (bottom) in the hippocampus (left) and amygdala (right). 

Should You Continue Eating Processed Foods? 

Although the study’s findings on DHA’s ability to combat diet-induced brain injury are promising, that doesn’t give us the green light to regularly chow down on our favorite processed foods. If people want to stay ahead of the aging game, they should look into eating more foods like salmon that are enriched with omega-3’s or maybe incorporate omega-3 supplements into their everyday diet. Either way, people must become aware of what they are putting inside their body. 

“These are the types of diets that are advertised as being low in fat, but they’re highly processed,” concluded Ruth Barrientos. “They have no fiber and have refined carbohydrates that are also known as low-quality carbohydrates. Folks who are used to looking at nutritional information need to pay attention to the fiber and quality of carbohydrates. This study really shows those things are important.” 


Michael J. Butler, Nicholas P. Deems, Stephanie Muscat, Christopher M. Butt, Martha A. Belury, Ruth M. Barrientos,Dietary DHA prevents cognitive impairment and inflammatory gene expression in aged male rats fed a diet enriched with refined carbohydrates, Brain, Behavior, and Immunity, Volume 98, 2021, Pages 198-209, ISSN 0889-1591,

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