Neurological resilience linked to ketogenic metabolism in stroke models

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Researchers from Voronezh State University in Voronezh and AN Belozersky Moscow State University in Moscow carried out experiments on mice to explore how a ketogenic diet might shield brain cells from paralysis-related damage. The study, supported by a grant from the Russian Science Foundation, appeared in Molecular Neurobiology.

In the experiment, 69 rodents were temporarily paralyzed to simulate stroke conditions and then assigned to three dietary groups. One group received a standard diet, a second followed a high-fat, low-carbohydrate ketogenic plan, and a third group consumed a standard diet supplemented with hydroxycitric acid. The feeding period lasted two weeks.

The ketogenic regimen appeared to preserve mitochondrial DNA integrity during stroke. Mitochondria, the energy powerhouses inside cells, are especially vulnerable to oxygen deprivation that occurs in stroke, making them a primary target for therapies aimed at reducing brain injury. With the ketogenic diet, fats became the main energy source, and ketone bodies were produced. At the same time, blood glucose levels declined, and gene activity in brain cells shifted, which is thought to support nerve cell recovery. While long-term adherence to a keto diet can bring risks for kidney and digestive health and is not suitable for everyone, researchers also investigated whether hydroxycitric acid might replicate some of the diet’s protective effects.

Hydroxycitric acid did not deliver the hoped-for protection. Instead, it worsened outcomes in several mice. About half of the animals in this group died within three days after the induced stroke. In the survivors, the extent of brain damage exceeded that seen in paralyzed mice that did not receive hydroxycitrate.

Researchers expressed surprise at the lack of protective impact from hydroxycitric acid, noting that dietary restrictions often associated with this compound have historically shown some brain protection in other contexts. Egor Plotnikov, who leads the RSF-supported project, commented that hydroxycitric acid carries potential side effects of particular concern. He added that such effects have been observed in some patients using the supplement for weight management, underscoring the need for caution and further study. The team’s findings contribute to a broader discussion about dietary strategies and brain resilience, emphasizing how metabolic shifts induced by fats and ketones may influence neural recovery mechanisms. The work also highlights the importance of understanding the nuanced roles of supplements in clinical contexts and the necessity of rigorous evaluation before translating these approaches to human patients.

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