Using mouse models of Alzheimer’s disease, researchers have been looking into a new approach to slow down the progression of this neurodegenerative disease — a ketone ester-rich diet.
To get the energy it needs to function correctly, the body usually relies on glucose (a simple sugar), which results from the digestion of carbohydrates.
When there is not enough glucose to rely on, the body will burn fat instead. This is a process called ketosis, and it is the principle that ketogenic — or keto — diets rely on.
Keto diets are typically low in carbohydrates and high in fats, and this imbalance in resources produces ketosis. But there is also another way of inducing ketosis that does not involve making this dietary shift. It involves taking supplements containing ketone ester, which have the same effect.
Researchers have also been interested in ketone ester because of the possibility that it may help fight neurodegenerative conditions, including Parkinson’s and Alzheimer’s disease.
Recently, a team of investigators from the Laboratory of Neurosciences at the National Institutes of Health (NIH) in Baltimore, MD — in collaboration with colleagues from other research institutions — has used mouse models of Alzheimer’s to further examine the potential of ketone ester, as well as the possible underlying mechanisms at work.
A study paper — whose first author is Aiwu Cheng, Ph.D., and which features in The Journal of Neuroscience — details the proceedings.
The researchers explain that early on in the development of Alzheimer’s disease, several changes occur in the brain. One of these changes is a lot more uncontrolled neural (brain cell) activity.
The investigators hypothesize that this lack of regulated brain cell activity may be due to damage to a set of specialized, inhibitory neurons — called GABAergic neurons. This means they are unable to prevent other brain cells from sending too many signals.
The study authors also suggest that since GABAergic neurons need more energy to function correctly, they may be more vulnerable to beta-amyloid, a protein that over accumulates in the brain in Alzheimer’s disease, becoming toxic.
According to existing studies, beta-amyloid also affects mitochondria, which are tiny organelles in cells that keep them “fuelled” with energy. Some researchers argue that beta-amyloid disrupts mitochondrial function by interfering with the SIRT3 protein that would usually help preserve it.
In their current study, the investigators genetically modified mouse models of Alzheimer’s disease, so that the rodents would produce lower than normal levels of SIRT3. They found that these mice experienced more violent seizures, had a higher rate of GABAergic neurons death, and were also more likely to die when compared both with healthy control mice and with regular Alzheimer’s disease model mice.
Yet, when the researchers fed the mice with lower SIRT3 levels a ketone ester-rich diet, the rodents did better, with fewer seizures and lower death rates.
Moreover, Cheng and the team also observed that a ketone ester-rich diet appeared to increase SIRT3 levels in the rodents that received it.
This has led the investigators to conclude that boosting SIRT3 levels by way of a ketone ester-rich diet may be useful in slowing down the progression of Alzheimer’s disease.