FREEDOM AND SAFETY
A low carb diet may prevent or even reverse the effects of aging in the brain, researchers report.
The new study also shows that the neurobiological changes associated with aging are evident in a person’s late 40s.
To better understand how diet influences brain aging, the research team focused on the presymptomatic period when prevention may be most effective. In the study, they show that functional communication between brain regions destabilizes with age, typically in the late 40’s. The study also shows that destabilization correlates with poorer cognition and accelerates with insulin resistance.
The researchers found that consumption of different fuel sources can reliably modulate this biomarker for brain aging. Glucose decreases the stability of brain networks. Ketones increase stability.
The researchers replicated this effect across both changes to total diet as well as after drinking a fuel-specific calorie-matched supplement.
“What we found with these experiments involves both bad and good news,” says lead author Lilianne R. Mujica-Parodi, a professor in the biomedical engineering department with joint appointments in the College of Engineering & Applied Sciences and Renaissance School of Medicine at Stony Brook University, and a faculty member in the Laufer Center for Physical and Quantitative Biology.
“The bad news is that we see the first signs of brain aging much earlier than was previously thought. However, the good news is that we may be able to prevent or reverse these effects with diet, mitigating the impact of encroaching hypometabolism by exchanging glucose for ketones as fuel for neurons.”
Using neuroimaging of the brain, researchers discovered that quite early on there is breakdown of communication between brain regions (“network stability”).
“We think that, as people get older, their brains start to lose the ability to metabolize glucose efficiently, causing neurons to slowly starve, and brain networks to destabilize,” says Mujica-Parodi.
“Thus, we tested whether giving the brain a more efficient fuel source, in the form of ketones, either by following a low-carb diet or drinking ketone supplements, could provide the brain with greater energy. Even in younger individuals, this added energy further stabilized brain networks.”
The researchers established brain network stability as a biomarker for aging by using two large-scale brain neuroimaging (fMRI) datasets totaling nearly 1,000 individuals, ages 18 to 88. They found that destabilization of brain networks was associated with impaired cognition and accelerated with type 2 diabetes, an illness that blocks neurons’ ability to effectively metabolize glucose.
To identify the mechanism as being specific to energy availability, the researchers then held age constant and scanned an additional 42 adults under the age of 50 years with fMRI. This allowed them to observe directly the impact of glucose and ketones on each individual’s brain.
The researchers tested the brain’s response to diet in two ways. The first was holistic, comparing brain network stability after participants had spent one week on a standard (unrestricted) vs. low carb (for example: meat or fish with salad, but no sugar, grains, rice, starchy vegetables) diet.
In a standard diet, the primary fuel metabolized is glucose, whereas in a low-carb diet, the primary fuel metabolized is ketones. However, there might have been other differences between diets driving the effects the researchers observed. Therefore, to isolate glucose vs. ketones as the crucial difference between the diets, they scanned an independent set of participants before and after drinking a small dose of glucose on one day, and ketones on the other, where the researchers had individually weight-dosed and calorically matched the two fuels. The results replicated, showing that researchers could attribute differences between the diets to the type of fuel they provide to the brain.
The study also shows that effects of brain aging emerged at age 47, with most rapid degeneration occurring at age 60. Even in younger adults, under age 50, dietary ketosis (whether achieved after one week of dietary change or 30 minutes after drinking ketones) increased overall brain activity and stabilized functional networks.
The researchers say the fact that ketones provide greater energy to cells than glucose, even with calorically matched fuels, may explain this. Research has previously show this benefits the heart, but the current set of experiments provides the first evidence for equivalent effects in the brain.
“This effect matters because brain aging, and especially dementia, are associated with ‘hypometabolism,’ in which neurons gradually lose the ability to effectively use glucose as fuel. Therefore, if we can increase the amount of energy available to the brain by using a different fuel, the hope is that we can restore the brain to more youthful functioning,” says Mujica-Parodi.
The research appears in PNAS.
Funding for the research came from the National Science Foundation and the W. M. Keck Foundation. Additional researchers are from Stony Brook, the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital and Harvard Medical School, Children’s National, the National Institutes of Health, and Oxford University.