Ketogenic diet may protect offspring from lasting prenatal stress impacts

A new study of young rats fed a ketogenic diet — high in fat and very low in carbohydrates — supports that it may protect from long-lasting prenatal stress from time spent in the womb.

In the trial, researchers stressed pregnant rats in the final week before birth. They weaned the offspring at 21 days after birth and assigned them either a control diet or a ketogenic diet.

They tested the young rats at 42 days for various stress-induced deficits, including poor sociability or lack of interest in their surroundings (anhedonia).

The animals that had received the ketogenic diet showed some notable differences over the control group, such as longer grooming times and greater sociability.

“The diet seems to have acted like a shield for their developing brains, preventing social and motivational problems from ever taking root,” says lead researcher Dr. Alessia Marchesin of the University of Milan, Italy.

“There are a couple of points to note. The animals on the ketogenic diet grew more slowly than the controls, and so it may be that the reduced calorie intake is associated with the later mental health benefits. And we see sex-specific differences that need to be better understood before we can apply this to humans.”

The researchers found that when fed a regular diet, 50% of the rats born to stressed mothers showed stress-related problems in later life. However, among rats fed a ketogenic diet, only 22% of male offspring and 12% of female offspring developed these problems.

Post-birth dietary interventions

The study builds on an extensive body of research, which has demonstrated that offspring can suffer ongoing psychological and development-related conditions if their mothers had experienced stress during pregnancy.

The researchers say their findings offer a “simple way” to prevent the occurrence of mood and social disorders that often originate from childhood adversity.

“Rather than waiting until symptoms appear and then treating them with medications — many of which carry side effects — we might one day take advantage of the therapeutic properties of dietary interventions early in life to prevent the manifestation of full-blown pathologic conditions,” says Marchesin.

Marchesin adds that her team found male and female rats benefited differently through biological routes — males by reducing inflammation and females by boosting antioxidant defences — hinting that such dietary interventions can be personalized.

“If these findings translate to humans, we may be able to treat the long-term burden of prenatal trauma simply by adjusting what at‑risk kids eat,” she notes.

Contributing to nutrition psychiatry

Previous research has supported the idea that the ketogenic diet induces various biological changes, such as enhancing mitochondrial efficiency and changing hormone balance.

Dr. Aniko Korosi, associate professor at the University of Amsterdam, the Netherlands, says the new research contributes further to the expanding field of nutritional psychiatry. “The role of nutrition in modulating mental health is gaining attention, and its potential is more and more appreciated in the field.”

One psychiatric investigation on the keto diet research published last month revealed that US college students experienced a 70% decrease in depression symptoms after sticking to a ketogenic diet for at least ten weeks.

Another clinical trial linked keto diets to “dramatic improvements” in metabolic function and psychiatric symptoms in overweight patients diagnosed with either bipolar disorder or schizophrenia.

“However, important questions remain in the field as to which nutrient, when, and for whom, is effective in modulating mental health,” notes Korosi. “The presented study interestingly shows that prenatal stress-induced risk to altered behavior can be modulated with a ketogenic diet fed after weaning.”

He adds it will be “intriguing to further explore what the biological processes involved in these beneficial effects are and if such effects are sex-specific.”

The new findings, which need confirmation in human studies, are being presented at the ongoing ECNP conference in Amsterdam (October 11–14).