A research team headed by University of Kentucky scientist Ai-Ling Lin has published two studies that demonstrate the effect of ketogenic diet (KD) — a high fat and low carbohydrate diet — on cognitive health in animals.
Ketogenic diet is characterized by high levels of fat and low levels of carbohydrates. Image credit: Robert Owen-Wahl.
The first study, published in the journal Scientific Reports, demonstrated that neurovascular function improved in mice who followed KD.
“Neurovascular integrity, including cerebral blood flow and blood-brain barrier function, plays a major role in cognitive ability,” Dr. 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 KD enhanced brain vascular function and reduced neurodegeneration risk in young healthy mice.”
In the study, two groups of nine young, healthy mice (12-14 weeks old) were given either KD or a regular diet.
After 16 weeks, the researchers 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, KD in particular, has demonstrated effectiveness in treating certain diseases, we chose to test healthy young mice using diet as a potential preventative measure,” Dr. Lin said.
“We were delighted to see that we might indeed be able to use diet to mitigate risk for Alzheimer’s disease.”
The beneficial effects seen from KD 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 KD, mTOR can also be inhibited by simple caloric restriction or the pharmaceutical rapamycin,” Dr. Lin said.
In the second study, published in the journal Frontiers in Aging Neuroscience, Dr. Lin and her colleagues used neuroimaging techniques to explore in vivo the effects of rapamycin, KD, 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,” Dr. Lin said.
“We speculated that neuroimaging might allow us to see those changes in the living brain.”
“Even more tantalizing: the 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.”
“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,” she said.
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David Ma et al. 2018. Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice. Scientific Reports 8, article number: 6670; doi: 10.1038/s41598-018-25190-5
Jennifer Lee et al. Neuroimaging biomarkers of mTOR inhibition on vascular and metabolic functions in aging brain and Alzheimer’s disease. Front. Aging Neurosci, published online July 26, 2018; doi: 10.3389/fnagi.2018.00225
