If you have ever dabbled in the world of dieting, you are likely to have stumbled across the famous ketogenic diet. But aside from melting fat and dropping pounds, this diet has been associated with improvements in brain health and longevity.
Now, new research has revealed how these beneficial effects might take place at a molecular level, at least in mice.
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"The ketogenic diet modifies the energy source for cells, replacing carbohydrates with fat," Christian González-Billault, a professor at the University of Chile and Buck Institute in California and director of the Geroscience Center for Brain Health and Metabolism, told Newsweek. "Such change induces a metabolic shift [...] corresponding to the state where cells maintain their functions on a new energy substrate, the fat."
In other words, this extreme restriction of dietary carbohydrates causes our body's cells to shift from using glucose as their primary source of fuel to using fat. This condition is known as ketosis.
To enter ketosis, carbohydrates must only make up about 5 percent of your daily calorie consumption.
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"Typical diets in the U.S. are around 50 percent calories from carbohydrate, so this is DRASTIC," Christopher Gardner, Rehnborg Farquhar professor of medicine and director of nutrition studies at the Stanford Prevention Research Center at Stanford University, previously told Newsweek.
"In order to be in ketosis, the emphasis needs to be on fat. A 'Well Formulated Ketogenic Diet' is around 75 percent fat. The typical American diet is around 35 percent fat, so this means more than a doubling of fat intake."
Despite the restrictive nature of this diet, as many as 7 percent of Americans followed the eating plan in 2022, according to data from the International Food Information Council. But, according to research in mice, the benefits of this metabolic shift may extend far beyond weight loss.
"Our work indicates that the effects of the ketogenic diet benefit brain function broadly, and we provide a mechanism of action that offers a strategy for the maintenance and improvement of this function during aging," González-Billault said.
In a new study, published in the journal Cell Reports Medicine, González-Billault and colleagues fed a group of aged mice a ketogenic diet and observed how it impacted their behavior and working memory.
On further investigation, the team saw that the mice on the ketogenic diet showed changes in the activity of the junctions between different cells in the brain involved in memory processing. Interestingly, these changes in activity appeared to be partially orchestrated by the molecules produced when the body goes into ketogenesis, known scientifically as ketone bodies.
"The results collected in our work provide a mechanistic explanation of the beneficial roles of the intermittent ketogenic diet in aged animals, which is an essential first step to understanding the molecular aspects responsible for the effect of this intervention," González-Billault said.
"We believe those effects might be related to maintaining capacities that naturally decrease during aging in aged individuals. In a sense, the resilience of the animals is increased, delaying the deleterious effects of aging on body functions."
However, it is so far unclear how translatable these findings are to humans.
"At this moment, these auspicious results in mice need further studies to address whether this intervention is suitable to improve human body functions," González-Billault said. "[The] high diversity and variability in humans related to genetic ancestry, genetic and non-genetic risk factors, lifestyle, the environment, education levels, and social and personal history make it challenging to propose one helpful, valuable strategy to all humans."
The keto diet is also not without its side effects.
"A chronic ketogenic diet, as opposed to our study using an intermittent ketogenic diet, might induce side effects due to the high consumption of fat, affecting the performance of critical organs such as the liver or increasing some cardiovascular risks due to imbalance in fatty acids and cholesterol," González-Billault said.
The restrictive nature of the diet also makes it difficult to stick to over a long period.
"For most people who try this diet, the success is short term," Gardner said. "It is so restrictive that most people can't maintain it long term."
However, González-Billault and his team hopes to isolate the molecules responsible for the memory improvements seen in their animal models to potentially provide the same results without the need for restrictive dieting.
"There are some strategies to circumvent some of these problems by providing ketone bodies instead of a high-fat diet, which merits further exploration to evaluate if this can be a strategy for improvement in humans in the long run," he said.
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