High-sugar diets may mimic Alzheimer’s pathology more closely than high-fat diets

A new study conducted on rodents suggests that while diets high in fat and diets high in sugar both lead to obesity and memory loss, they may damage the brain through different biological pathways. The researchers discovered that only chronic sugar consumption resulted in the accumulation of amyloid beta, a protein hallmark of Alzheimer’s disease, within the energy centers of brain cells. These findings were published in the journal Nutritional Neuroscience.

Obesity is a growing global health concern that carries risks extending beyond cardiovascular disease and diabetes. Medical professionals recognize a strong link between metabolic disorders and the decline of cognitive functions. This connection is often characterized by a state of chronic, low-grade inflammation and oxidative stress throughout the body.

The brain is particularly sensitive to these metabolic disturbances. To function correctly, brain cells rely on mitochondria. These microscopic structures act as power plants within the cell to generate energy. When mitochondria malfunction, they can produce harmful byproducts known as reactive oxygen species.

This oxidative stress can damage neurons and has been linked to the production of amyloid beta peptide. In patients with Alzheimer’s disease, this peptide clumps together to form toxic plaques between nerve cells. It also accumulates inside the mitochondria themselves, where it disrupts energy production and triggers cell death.

While the association between obesity and neurodegeneration is established, the specific dietary components driving this damage remain under investigation. A research team from the Universidad Autónoma Metropolitana and the Universidad Juárez Autónoma de Tabasco in Mexico sought to clarify this relationship. They aimed to determine whether fat or sugar acts as the primary driver for these specific brain changes.

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The researchers designed a long-term experiment using male Wistar rats. They divided the animals into three distinct groups to observe the effects of chronic consumption over a period of twelve months. The control group ate standard laboratory food and drank purified water.

The second group received a high-sucrose diet. These animals had access to the standard food but drank a thirty percent sucrose solution instead of water. This mimics a diet heavy in sugary beverages.

The third group consumed a high-fat diet. Their food was enriched with lard so that fat comprised thirty percent of their total intake. This was intended to replicate a diet rich in saturated animal fats.

After one year, the team assessed the animals’ physical health and cognitive abilities. They measured body weight, body fat distribution, and blood pressure. They also analyzed blood samples to check for glucose, cholesterol, and triglycerides.

The physical results showed that both the high-fat and high-sugar groups developed central obesity. While their total body weight was not statistically different from the control group, they carried significantly more abdominal fat. Both groups also developed high systolic blood pressure.

The metabolic effects differed slightly between the two experimental diets. The rats fed the high-fat diet exhibited elevated fasting glucose levels. This suggests a disruption in how their bodies managed blood sugar at rest.

In contrast, the rats on the high-sugar diet showed signs of insulin resistance. When given a glucose tolerance test, their bodies struggled to clear sugar from the blood efficiently over time. This group also displayed significantly higher levels of triglycerides.

To evaluate brain function, the researchers utilized the Morris water maze. This is a standard behavioral test where rats must swim in a pool to find a hidden platform. It assesses spatial memory and learning capabilities.

The cognitive results were concerning for both experimental groups. Rats fed either the high-fat or high-sugar diet took approximately twice as long to locate the safety platform compared to the control group. This indicates a significant decline in spatial memory regardless of the specific diet type.

Following the behavioral tests, the researchers analyzed brain tissue from the hippocampus and the cerebral cortex. These areas are critical for memory and learning and are often the first to be affected by Alzheimer’s disease. The team separated the mitochondria from the rest of the cell tissue to examine them specifically.

They tested for markers of oxidative stress, specifically looking for damage to lipids and proteins. Both diets caused significant damage to the mitochondrial membranes in the hippocampus. The fats and proteins within these cellular structures showed chemical signs of oxidation, similar to rusting.

The study then examined the activity of the electron transport chain. This is the series of protein complexes within mitochondria that actually produces energy. The activity of these complexes was altered in both diet groups, suggesting the brain cells were struggling to maintain energy levels.

The most distinct finding appeared when the researchers measured amyloid beta levels. They looked for this toxic peptide in both the general cell fluid and specifically inside the mitochondria. In the high-fat group, there was no significant increase in mitochondrial amyloid beta.

However, the high-sugar group told a different story. These animals showed a marked accumulation of amyloid beta peptide within the mitochondria of both the hippocampus and the cerebral cortex. This suggests that high sugar intake triggers a specific pathological pathway that closely resembles the molecular signature of Alzheimer’s disease.

This accumulation of amyloid beta is significant because the peptide is known to disrupt mitochondrial function physically. It can block the transport of essential proteins and alter the enzymes necessary for energy production. The presence of this peptide in the sugar-fed rats correlates with the unique metabolic damage observed in that group.

The authors suggest that while both diets lead to obesity and memory loss, the mechanisms differ. The high-fat diet appears to cause damage through general oxidative stress and inflammation. The high-sucrose diet involves these factors but also specifically promotes the buildup of neurodegenerative proteins.

The study indicates that fructose, a component of sucrose, may be particularly toxic to brain cells. The metabolism of fructose generates distinct byproducts that can lead to rapid cellular damage. This may explain why the amyloid accumulation was specific to the sugar-fed group.

There are caveats to this research that must be considered. The study was conducted on rats, and human metabolism and brain function are more complex. The results observed in animal models do not always translate directly to human clinical outcomes.

Additionally, the experimental diets were somewhat unbalanced regarding protein intake. The addition of lard or sugar reduced the overall percentage of protein the rats consumed. It is possible that protein deficiency contributed partially to the observed negative health effects.

Future research is needed to explore whether these changes are reversible. Scientists need to determine if returning to a healthy diet can clear the accumulated amyloid beta. There is also interest in whether antioxidant treatments could mitigate the mitochondrial damage caused by these diets.

The team also highlighted the potential role of “vitagenes,” which are genes involved in the cellular stress response. Activating these genes might offer a way to protect neurons from diet-induced damage. Understanding these pathways could lead to new preventive strategies for neurodegenerative diseases.

Ultimately, this research provides evidence that not all calories affect the brain in the same way. While preventing obesity is important for general health, limiting sugar intake may be specifically relevant for Alzheimer’s prevention. The data reinforces the importance of diet quality over simple calorie counting.

As the authors state in their conclusion: “With these findings, we show that, although excessive consumption of fat or sucrose drives to obesity, only the last could potentially bridge the gap between obesity and neurodegenerative pathogenesis, thereby highlighting the relevance of lifestyle and diet quality, bringing a way to develop preventive strategies.”

The study, “Obesity and Alzheimer´s disease: unraveling the impact of chronic consumption of high-fat or high-sucrose diets on neurodegeneration and mitochondrial dysfunction,” was authored by Carlos Francisco Aguilar Gamas, Norma Edith López Diaz-guerrero, Nancy Patricia Gómez-Crisóstomo, Erick Natividad De la Cruz-Hernández, Cecilia Zazueta, Ixchel Ramírez-Camacho, Corazón de María Márquez-Álvarez, and Eduardo Martínez-Abundis.