Scientists find eating refined foods for just three days can impair memory in the aging brain

A new study published in Brain, Behavior, and Immunity provides evidence that consuming refined diets for as little as three days can lead to memory impairments in the aging brain. The research suggests that the removal of dietary fiber, a common characteristic of refined foods, may trigger rapid disruptions in brain cell energy production and inflammatory signaling, particularly in the the amygdala, a brain region central to processing fear and emotional memories.

The motivation behind this investigation stems from a need to disentangle the specific nutritional components that contribute to cognitive decline. Previous experiments have frequently utilized high-fat diets to model poor nutrition.

But these experimental diets often differ from standard control diets in multiple ways, including sugar content, protein sources, and fiber levels. Consequently, it remained unclear whether dietary fat, added sugar, or a combination of both drives the memory deficits observed in earlier work.

“Previous research, including our own, has shown that so-called ‘high-fat diets’ can impair memory very quickly, within just a few days, especially in older animals and people. The problem is that the term ‘high-fat diet’ is vague,” explained study authors Ruth M. Barrientos, an associate professor, and Kedryn K. Baskin, an assistant professor, both at The University of Ohio.

“These diets often differ not just in fat, but also in how much sugar and other nutrients they contain. Because of this, it hasn’t been clear whether fat, sugar, or some combination of the two is actually responsible for the memory deficits that have been reported.”

“To address this gap, we designed a study that allowed us to isolate these nutrients more precisely. We used carefully controlled, refined diets that contained specific amounts of fat, sugar, and protein, without the extra components normally found in standard diets. This allowed us to directly compare the effects of high versus low saturated fat and sugar, both alone and together, against a typical low fat, low sugar grain-based diet.”

The researchers utilized male rats at two distinct life stages: young adults at three months old and aged rats at twenty-four months old. The sample size included groups of four to eight animals per condition for various biological and behavioral assays. The animals were assigned to one of several dietary groups for a period of three days.

One group received standard laboratory chow, which is high in fiber and complex carbohydrates. Other groups received purified, refined diets that varied in their composition. These included a low-fat low-sugar diet, a low-fat high-sugar diet, and a high-fat low-sugar diet. A critical feature of all the refined diets was the exclusion of dietary fiber.

To assess memory function, the team employed a fear conditioning procedure. After three days on their respective diets, the rats were placed in a specific chamber where they heard a tone followed by a mild foot shock. This created an association between the environment, the tone, and the negative stimulus.

The researchers tested the rats’ memory four days later. They placed the animals back in the original chamber to test “contextual fear memory,” which relies heavily on the hippocampus. They also placed the rats in a new environment but played the tone to test “cued-fear memory,” which relies heavily on the amygdala.

“By testing both young and aged rats and examining different types of memory, we aimed to better understand which parts of the diet matter most for brain health, and whether age makes the brain more vulnerable to certain nutrients,” Barrientos and Baskin explained.

The behavioral assessments revealed a clear distinction between age groups. Young rats maintained intact memory function across all diet types, showing no significant deficits in freezing behavior when exposed to the context or the tone. In contrast, the aged rats displayed significant vulnerabilities.

The results indicated that aged rats fed the high-fat, low-sugar refined diet exhibited impairments in hippocampal-dependent memory. This group showed reduced freezing behavior when returned to the original chamber compared to those fed standard chow. However, the results regarding the amygdala were even more broad.

Aged rats across all refined diet groups showed significant impairments in amygdala-dependent memory. Regardless of whether the diet was high in fat or high in sugar, the animals failed to freeze in response to the tone as effectively as the control group. This suggests that the aged amygdala is sensitive to the general composition of refined diets rather than a single macronutrient like fat.

“We were surprised at how quickly these effects were observed (3 days) after eating these diets, suggesting that reaching a state of obesity isn’t necessary to see significant effects to brain health and function.”

Beyond behavior, the investigators examined the biological machinery within the brain cells. They extracted mitochondria, the energy-producing powerhouses of the cell, from the hippocampus and amygdala tissues. Using a technique called respirometry, they measured how much oxygen the mitochondria consumed to produce energy.

The analysis showed that mitochondria in the amygdala of aged rats functioned less efficiently after consuming any of the refined diets. These organelles exhibited reduced oxygen consumption at baseline and when stimulated with specific energy substrates. This metabolic suppression mirrored the behavioral deficits observed in the cued-fear tasks.

Similar mitochondrial dysfunction was observed in the hippocampus of aged rats. While the behavioral deficits in this region were limited to the high-fat group, the metabolic data indicated that refined diets generally compromised mitochondrial respiration in this area as well. Young rats, however, showed preserved mitochondrial function, suggesting their brains possess compensatory mechanisms that protect them from short-term dietary stress.

Further investigation focused on specific types of brain cells isolated from the tissue. The researchers examined microglia, the brain’s primary immune cells, and astrocytes, which support neuronal health. The data revealed that microglia from aged rats were particularly susceptible to the dietary challenge.

Microglia isolated from aged rats on refined diets exhibited a widespread suppression of mitochondrial respiration. They appeared metabolically rigid and unable to adapt to changing energy demands. In contrast, microglia from young rats retained metabolic flexibility, showing the ability to increase activity when necessary.

Astrocytes from aged rats showed more specific impairments. While they maintained baseline energy production, they exhibited deficits when their maximal capacity was tested. Interestingly, the data suggested that aged astrocytes might increase their reliance on glycolysis, an alternative method of energy production, potentially as a coping mechanism.

The researchers also analyzed the contents of the rats’ guts and blood to explore potential causes for these brain changes. A common characteristic of all the refined diets used in the experiment was a deficiency in dietary fiber. Fiber is fermented by gut bacteria to produce short-chain fatty acids, such as butyrate.

The data showed a rapid and significant depletion of butyrate in the cecum and blood serum of rats fed refined diets. This drop occurred within just three days. Aged rats had lower baseline levels of butyrate compared to young rats, and the dietary intervention exacerbated this deficiency.

Butyrate is known to support mitochondrial function and control inflammation. The statistical analysis revealed a correlation between low circulating butyrate levels and the severity of memory impairment in the aged animals. This provides a plausible link between the lack of dietary fiber and the observed cognitive deficits.

Finally, the researchers analyzed the protein composition within the brain regions using proteomic techniques. This analysis identified broad changes in protein expression in the aged amygdala and hippocampus following refined diet consumption. Specifically, proteins related to mitochondrial structure and synaptic signaling were altered.

In the hippocampus, the diets affected pathways involved in sirtuin signaling, which regulates cellular health and energy. In the amygdala, the refined diets influenced pathways related to axon guidance and the formation of synapses. These molecular changes align with the functional deficits seen in the mitochondrial assays and behavioral tests.

“Our study shows a few key things,” Barrientos and Baskin told PsyPost. “Older animals that ate the high-fat, low sugar refined diet showed problems with memory linked to the hippocampus, the part of the brain involved in things like navigation and remembering events. But even more striking, all of the refined diets we tested, regardless of fat or sugar content, impaired the aged rats’ emotional memory, memory linked to the amygdala, which helps us learn from fearful or dangerous experiences.”

“These findings suggest that eating these diets may make it harder for older adults to recognize and remember situations that could be harmful, which could increase the risk of physical accidents or even financial mistakes. The common thread across these refined diets was a lack of fiber, making them very similar to ultra-processed foods.”

“At a biological level, we found that these diets interfere with how mitochondria within brain cells of aged rats produce and manage energy,” the researchers explained. “The biggest effects were seen in microglia, the brain’s immune cells, which became less flexible to changing energy demands. Importantly, low-fiber diets caused a sharp drop in butyrate, a helpful substance produced by gut bacteria when we eat fiber. This suggests that fiber plays a crucial role in supporting brain energy use and memory, (but this still needs to be tested).”

While the study provides detailed insights into the effects of refined diets, there are limitations to consider. The experiments were conducted exclusively on male rats, meaning the results may not fully apply to females. Hormonal differences can influence metabolic and immune responses, warranting similar studies in female subjects.

Additionally, while the study establishes a strong association between low butyrate levels and memory loss, it does not definitively prove causation. Future research will need to determine if supplementing fiber or butyrate can prevent or reverse the memory impairments caused by refined diets. The current findings focus on short-term exposure, and longer-term studies would be necessary to see if these deficits persist or worsen over time.

“We still need to determine whether supplementing unhealthy refined diets with fiber or butyrate, the metabolite of fiber, is sufficient to restore memory function,” Barrientos and Baskin said.

The study, “The aged amygdala’s unique sensitivity to refined diets, independent of fat or sugar content: A brain region and cell type-specific analysis,” was authored by Michael J. Butler, Jade A. Blackwell, Andrew A. Sanchez, Hannah F. Sanders, Dominic W. Kolonay, Jeferson Jantsch, Stephanie M. Muscat, Maria Elisa Caetano-Silva, Akriti Shrestha, Casey Kin Yun Lim, Sabrina E. Mackey-Alfonso, Bryan D. Alvarez, Robert H. McCusker, Jacob M. Allen, Kedryn K. Baskin, and Ruth M. Barrientos.