Study Reveals Exercise's Unexpected Benefits for Brain Health

A recent study conducted by researchers at the University of Missouri Columbia has uncovered significant insights into the relationship between regular endurance exercise and brain health, particularly in the context of liver function and ketone production. The findings suggest that exercise can enhance cognitive function even when the liver's ability to produce ketones—an important energy source for the brain—is compromised.

The research, published in the Journal of Physiology in July 2025, highlights the critical role that ketones play in brain energy metabolism. Typically, the brain relies heavily on glucose for energy; however, during periods of fasting or intense physical activity, the liver produces ketones to serve as an alternative energy source. These ketones are vital for cognitive functions such as memory, learning, and overall brain health.

In the study, researchers blocked ketone production in healthy young female rats by inhibiting the liver enzyme HMGCS2, which is essential for ketogenesis. Following this, the rats were subjected to either a single session of running or a regimen of treadmill training over four weeks. Surprisingly, while the rats with reduced ketone production exhibited impaired brain function—indicated by diminished mitochondrial activity and poorer performance on memory tests—those that engaged in regular exercise demonstrated improved cognitive outcomes despite their ketone deficiency.

Postdoctoral fellow Taylor Kelty, a key researcher in this study, remarked, "Going into the study, we thought that with fewer ketones and the cognitive impairments that causes, exercise may not be able to overcome that impairment. But it seems like exercise is so powerful that there are other mechanisms going on in the brain that allow it to circumvent those impairments and still receive the benefits from exercise." This underscores the multifaceted nature of exercise's impact on brain health, suggesting that even when one biochemical pathway is disrupted, others may compensate to uphold cognitive function.

The implications of this research extend beyond laboratory settings. Given the increasing prevalence of liver diseases, which can hinder ketone production and lead to cognitive decline, these findings offer hope for individuals at risk of memory-related disorders. Kelty noted, "If ketone production in the liver is disrupted, it could be a potential cause of cognitive decline, ultimately leading to conditions like dementia."

Moreover, Professor R. Scott Rector, who co-led the research, emphasized the need for further investigation into how various bodily systems interact, particularly the liver-brain axis. He stated, "This study highlights how exercise benefits the body in a multitude of ways, even when we don’t fully understand all the molecular mechanisms involved."

While the study primarily focused on animal models, the researchers hope to translate these findings to human populations, especially as the number of people expected to develop Alzheimer’s disease more than doubles by 2060, according to estimates from the Centers for Disease Control and Prevention.

The study's results reinforce the long-held belief among health professionals that regular physical activity holds significant benefits for brain health. As exercise promotes better blood circulation and enhances brain cell repair, its role in maintaining cognitive function becomes even more critical, particularly for those with underlying health conditions. In conclusion, the research indicates that regular endurance exercise could serve as a powerful preventive measure against cognitive decline, providing a promising avenue for future studies aimed at preserving brain health as individuals age. The researchers are optimistic about the potential for their work to inform strategies that help mitigate the cognitive impacts of liver-related health issues, ultimately benefiting public health outcomes.

As the field of liver-brain research grows, understanding the intricate connections between these systems may lead to new preventive strategies against memory loss and cognitive decline, thereby enabling individuals to maintain cognitive health well into old age.