Theme Food I: How energy molecules affect aging brains

Scientists are searching to uncover how molecules related to our energy production in the body may influence brain health as we age. What is healthy for our brains?

In human energy production, ketone bodies, pyruvate, and citrate are vital for the delivery of energy to the cells in our body - and they are linked to our diet.

Ketone bodies are produced during fat metabolism, especially in fasting and when eating fewer carbs, such as in ketogenic diets.

Pyruvate is a product of carbohydrate breakdown and comes from starchy foods like bread. Citrate, found naturally in citrus fruits, supports energy metabolism as part of the citric acid cycle in cells.

The study
Researchers studied these key metabolites in blood samples from nearly 1,850 older adults who were part of a long-term health study.

Besides blood blood samples, their cognitive abilities were assessed over nine years of study. Brain imaging was conducted during the research period. By analyzing these metabolites, the team sought to understand their links to memory decline, changes in brain structure, and the risk of developing dementia.

The findings of the study were that higher levels of ketone bodies (particularly a molecule called beta-hydroxybutyrate) were linked to faster cognitive decline and an increased likelihood of dying from dementia.

Conversely, higher levels of pyruvate, another molecule central to our natural energy production, were connected to better brain outcomes, including slower memory decline. With higher levels of pyruvate, people had smaller brain ventricles.

The brain ventricles are a set of hollow spaces inside the brain that are filled with fluid. This fluid helps protect the brain, remove waste, and keep it cushioned. These fluid-filled spaces normally increase in size when aging, as the brain tissue gradually shrinks.

So, a smaller size of the brain ventricles suggests less tissue loss and a reduced risk of dementia.

Citrate, a molecule involved in cellular energy cycles, also appeared to have protective effects, with higher levels associated with slower cognitive decline and lower dementia risk.

So - while ketone bodies may have adverse effects in this context, pyruvate and citrate seem to offer some protection against cognitive decline and dementia.

These findings could pave the way for new strategies to preserve brain health through better understanding and potential regulation of these metabolites.

Until then, enjoy a balanced and moderate diet that works for your needs—not too much, not too little.

About the scientific paper:

First author: Laia Gutierrez-Tordera, Spain
Published: Aging and Disease. November 2024.
Link to paper: https://www.aginganddisease.org/EN/10.14336/AD.2024.0754