Share on Pinterest A ketogenic diet may help maintain brain health in old age, but why? A new study in mice sheds new light on the question. Image credit: d3sign/Getty Images. Studies have already shown that a ketogenic diet can improve brain performance in old male mice. Now, the authors of a new mouse study have identified a specific mechanism that may underlie this phenomenon. The study raises questions about the role of diet in aging and brain health.
Researchers have discovered a potential mechanism underlying the improvements seen in older male mice following a ketogenic diet (or “keto diet” for short).
They claim that feeding male mice alternating between a control and a ketogenic diet improves the signaling that occurs between synapses in the brain.
Previously, one of the paper's authors, John Newman, MD, PhD, published a proof-of-concept study showing that putting male mice on a cyclical ketogenic diet reduced their risk of death in midlife and prevented the memory decline associated with normal aging.
“We decided to study the effects of the ketogenic diet after reading two seminal papers published in 2017 showing a beneficial role for the overall health of aged mice, including brain function,” Christian Gonza-Les Billot, lead author of the new study on ketogenic diet and aging, professor at the University of Chile, director of the Gerontological Center for Brain Health and Metabolism (GERO), and adjunct professor at the Buck Institute for Aging Research, told Medical News Today.
“These two [previous] “In this study, the authors showed improvements in specific behavioral tasks routinely used in animal studies to assess memory and learning,” he continued.
“These improvements made us decide to look deeper into the molecular mechanisms that explain that positive response on the one hand, and to include several other assessments at different levels, from the whole organism level to molecular functions, to understand why this diet was beneficial for older animals,” added Gonza-Les-Billot, who collaborated with Newman on the recent study.
The team's latest findings are published in Cell Reports Medicine.
To further explore their previous findings, the researchers placed 19 male mice aged 20 to 23 months, considered “old” in mice, on either a control diet or a ketogenic diet with the control diet repeated every two weeks.
Metabolic parameters of these mice were measured for the first 12 weeks, and then the mice were fed the diet and behavioral tests were performed for the next five weeks.
Results showed that the ketogenic diet was associated with lower blood sugar levels and improved memory and motor skills in the aged mice. The researchers showed increased plasticity in the hippocampus region of the brain in the aged mice.
Further testing revealed that the increased plasticity seen in the mice alternating between a ketogenic and control diet was due to molecules called ketones, which are produced when blood sugar levels are low, activating signaling pathways between synapses.
“We focused on older mice because previous studies have shown that the effects of diet in younger animals were milder and in some cases not significantly different from a control diet. These previous examples suggest that one beneficial role of diet may be to maintain resilience in older mice and improve age-related physiological functions,” said Gonzalez-Billot.
“This concept is fundamental in the field of aging because it has to do with the difference between lifespan (the entire trajectory of life from birth to death) and healthspan (the part of the trajectory of life that is free of chronic diseases),” he explained.
As for why the keto diet may not have the same effect on younger people, the researchers point out:
“Why this doesn't happen when animals are young deserves further study. However, we can speculate that the internal recovery mechanisms that are present when young may be sufficient to compensate or overcome the damage induced to cells, tissues, organs and organisms.”
In addition to animal studies, small human studies also suggest that the keto diet may benefit cognitive function, especially in older adults with dementia.
These mechanisms may be similar to those identified in animal studies, such as reduced inflammation, improved blood sugar control, and the potential of ketones to support brain function, but research is still in its early stages and larger clinical studies are needed to confirm these potential benefits.
One of the limitations of the ketogenic diet, besides the lack of robust human studies, is that it can be difficult to adhere to, with many people struggling without carbohydrates in their diet.
Because the ketogenic diet significantly reduces carbohydrate intake, it also reduces the intake of plant-based foods, which can result in reduced intake of fiber, vitamins, minerals, and antioxidants that are important for overall health.
Instead of the keto diet, experts generally recommend that older adults follow diets that are backed by more extensive human research for healthy aging.
The Mediterranean diet and the DASH diet are two of the most recommended and scientifically supported diets for healthy aging.
If you want to try a ketogenic diet, it's best to do so under the supervision of a doctor or registered dietitian to ensure adequate nutrition and optimal health.
This study and previous studies looked specifically at male mice.
“We decided to first examine the effects of the intervention in male mice, because using a separate sex increases the power of comparison. We cannot scrutinize the effects on the entire population, which is part of the limitations of our study. However, the effects observed in this study make it worth further evaluating the impact of the ketogenic diet on female mice,” explained Gonzalez-Billot.
Because women's metabolism processes fat differently than men's, questions have been raised in the past about the effectiveness of the ketogenic diet in women, and this is now the focus of ongoing research.
However, this means that not only was the study carried out in mice, which limits its applicability to understanding the ketogenic diet in humans, but it was also limited in its applicability across biological sexes, as it was only conducted in men.
Gonza Lez Billot agreed that further research into the discovery is definitely needed.
“In our next studies, we aim to gain a deeper understanding of the molecular mechanisms involved in the beneficial role of diet in aged mice. We want to elucidate whether these effects observed in the brain are solely due to the brain itself, or whether some of the responses we evaluate are linked to more systemic effects or even to the function of other relevant organs. Furthermore, we want to gain a deeper understanding of the metabolic changes that improve brain function at a cellular level,” he said.
Other experts agree that the study offers intriguing findings, but stress that further human studies are needed to confirm these effects.
Katherine Lal, a Denver, Colorado-based registered dietitian and certified nutritionist for Happy V, who was not involved in the study, said:
“This study suggests that repeated short-term use of a keto diet may benefit memory, motor function, and neuroplasticity, but does not specifically show why. Of note, this study was conducted in male mice, so its applicability to humans in general, and women in particular, is limited.”
