Study: Ketogenic diet appears to prevent cognitive decline in mice

October 12, 2018, University of Kentucky
PET scan of a human brain with Alzheimer's disease. Credit: public domain

We've all experienced a "gut feeling"—when we know deep down inside that something is true. That phenomenon and others (like "butterflies in the stomach") aptly describe what scientists have now demonstrated: that the gut and the brain are more closely connected than we once thought, and in fact the health of one can affect the other.

Capitalizing on this relatively new scientific concept, Ai-Ling Lin and her colleagues at the Sanders-Brown Center on Aging at the University of Kentucky have published two studies that demonstrate the effect of on cognitive health in animals.

The first, in Scientific Reports, demonstrated that neurovascular function improved in mice who followed a Ketogenic Diet regimen.

"Neurovascular integrity, including and blood-brain barrier function, plays a major role in cognitive ability," Lin said. "Recent science has suggested that neurovascular integrity might be regulated by the bacteria in the gut, so we set out to see whether the Ketogenic Diet enhanced brain vascular function and reduced neurodegeneration risk in young healthy mice."

Lin et al considered The Ketogenic Diet—characterized by high levels of fat and low levels of carbohydrates—a good candidate for the study, as it has previously shown positive effects for patients with other neurological disorders, including epilepsy, Parkinson's disease, and autism. Two groups of nine mice, aged 12-14 weeks, were given either the Ketogenic Diet (KD) or a regular diet. After 16 weeks, Lin et al saw that the KD mice had significant increases in cerebral blood flow, improved balance in the microbiome in the gut, lower blood glucose levels and body weight, and a beneficial increase in the process that clears amyloid-beta from the brain—a hallmark of Alzheimer's disease.

"While diet modifications, the Ketogenic Diet in particular, has demonstrated effectiveness in treating certain diseases, we chose to test healthy young mice using diet as a potential preventative measure," Lin said. "We were delighted to see that we might indeed be able to use diet to mitigate risk for Alzheimer's disease."

According to Lin, the beneficial effects seen from the Ketogenic Diet are potentially due to the inhibition of a nutrient sensor called mTOR (mechanistic target of rapamycin), which has shown to effect lifespan extension and health promotion. In addition to the Ketogenic Diet, Lin said, mTOR can also be inhibited by simple or the pharmaceutical rapamycin.

The second study, published in Frontiers in Aging Neuroscience, used neuroimaging techniques to explore in vivo the effects of rapamycin, the Ketogenic Diet, or simple caloric restriction on the cognitive function of both young and aging mice.

"Our earlier work already demonstrated the positive effect rapamycin and caloric restriction had on neurovascular function," Lin said. "We speculated that neuroimaging might allow us to see those changes in the living brain."

Even more tantalizing: her data suggested that caloric restriction functioned as a sort of "fountain of youth" for aging rodents, whose neurovascular and metabolic functions were better than those of young mice on an unrestricted diet.

Lin emphasizes that it's too early to know whether the regimens will confer the same benefit in humans, but since rapamycin and other mTOR inhibitors have already been approved by the FDA and are widely prescribed for other diseases, it's realistic to think that study in humans could follow relatively quickly.

Linda Van Eldik, Ph.D., Director of the UK Sanders-Brown Center on Aging, said that Lin's work justifies a transition to similar studies in humans, since all of the methods Lin used in animal models can be readily applied to humans.

"Ai-Ling's lab was the first to use neuroimaging to see these changes in a living brain, and the potential link to changes in the gut microbiome," she said. "Her work has tremendous implications for future clinical trials of neurological disorders in aging populations."

Lin and her lab are already doing just that; designing a clinical trial to understand the role of the gut microbiome in neurovascular dysfunction (a risk factor for AD) and in healthy aging.

"We will use neuroimaging to identify the association between gut microbiome balance and brain vascular function in individuals over 50 years of age, with an ultimate goal to design and test nutritional and pharmacological interventions that will prevent Alzheimer's disease," she said.

Explore further: Studies show connection between diet, cognitive function

More information: Jennifer Lee et al, Neuroimaging Biomarkers of mTOR Inhibition on Vascular and Metabolic Functions in Aging Brain and Alzheimer's Disease, Frontiers in Aging Neuroscience (2018). DOI: 10.3389/fnagi.2018.00225

Related Stories

Studies show connection between diet, cognitive function

October 2, 2018
We've all experienced a "gut feeling"—when we know deep down inside that something is true. That phenomenon and others, aptly describe what scientists have now demonstrated: that the gut and the brain are more closely connected ...

Animal study suggests ketone supplement more effective for weight loss

October 4, 2018
New study suggests ketone supplement more effective than low-carbohydrate, high-fat ketogenic diets at reducing body weight in mice

Ketogenic diet improves healthspan and memory in aging mice

September 5, 2017
A ketogenic diet significantly improved memory in aging mice and increased the animal's chances of surviving to old age. Results of the study from Eric Verdin's lab at the Buck Institute for Research on Aging in Novato, CA ...

Eat fat, live longer? Mouse study shows a high fat diet increases longevity, strength

September 5, 2017
As more people live into their 80s and 90s, researchers have delved into the issues of health and quality of life during aging. A recent mouse study at the UC Davis School of Veterinary Medicine sheds light on those questions ...

Caloric restriction in combination with low-fat diet helps protect aging mouse brains

March 12, 2018
A low-fat diet in combination with limited caloric consumption prevents activation of the brain's immune cells—called microglia—in aging mice, shows research published today in Frontiers in Molecular Neuroscience. The ...

As the keto diet gains popularity, scientists explain what we do and don't know

August 30, 2018
As Silicon Valley trendsetters, famous actors, and online health sites tout the low-carbohydrate, high-fat ketogenic, or "keto," diet, scientists are working to study it – from how it impacts inflammation in the brain to ...

Recommended for you

Wiring diagram of the brain provides a clearer picture of brain scan data

December 14, 2018
Already affecting more than five million Americans older than 65, Alzheimer's disease is on the rise and expected to impact more than 13 million people by 2050. Over the last three decades, researchers have relied on neuroimaging—brain ...

Scientists identify method to study resilience to pain

December 14, 2018
Scientists at the Yale School of Medicine and Veterans Affairs Connecticut Healthcare System have successfully demonstrated that it is possible to pinpoint genes that contribute to inter-individual differences in pain.

Parents' brain activity 'echoes' their infant's brain activity when they play together

December 13, 2018
When infants are playing with objects, their early attempts to pay attention to things are accompanied by bursts of high-frequency activity in their brain. But what happens when parents play together with them? New research, ...

In the developing brain, scientists find roots of neuropsychiatric diseases

December 13, 2018
The most comprehensive genomic analysis of the human brain ever undertaken has revealed new insights into the changes it undergoes through development, how it varies among individuals, and the roots of neuropsychiatric illnesses ...

Researchers find the cause of and cure for brain injury associated with gut condition

December 13, 2018
Using a mouse model of necrotizing enterocolitis (NEC)—a potentially fatal condition that causes a premature infant's gut to suddenly die—researchers at Johns Hopkins say they have uncovered the molecular causes of the ...

Researchers discover abundant source for neuronal cells

December 13, 2018
USC researchers seeking a way to study genetic activity associated with psychiatric disorders have discovered an abundant source of human cells—the nose.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.