Ketogenic diet may protect against stress experienced in the womb

Researchers have shown that young rats fed a ketogenic diet—a diet with high fat and low carbohydrates—are protected from the lasting experience of pre‑natal stress. This work, which has not yet been confirmed in humans, was presented at the ECNP conference in Amsterdam.

An extensive body of research has shown that if mothers experience stress while pregnant, the offspring can suffer ongoing psychological and development‑related conditions.

Now Italian researchers have shown that the biological changes induced by a ketogenic diet may help them to escape from the long‑lasting effects of stress experienced in the womb.

The pregnant rats were stressed in the final week before birth. The offspring were weaned at 21 days after birth, and assigned either a control diet, or a ketogenic diet. At 42 days, the young animals were then tested for a variety of stress‑induced deficits, such as poor sociability, or lack of interest in their surroundings (anhedonia).

The animals who had received the ketogenic diet showed some notable differences over the control group, such as exhibiting longer grooming times, and greater sociability. The researchers found that in the stressed mothers fed a normal diet, 50% of the rats born to them showed stress‑related problems in later life. However, in those rats fed a ketogenic diet, only 22% of male offspring and 12% of female offspring developed these problems.

The ketogenic diet has been shown to induce a variety of biological changes, such as enhancing mitochondrial efficiency and changing hormone balance.

According to lead researcher Dr. Alessia Marchesin (of the University of Milan), “We discovered that feeding young rats a ketogenic diet—a high‑fat, very low‑carbohydrate regimen—right after weaning almost completely protected them from the lasting effects of stress they’d experienced before birth. The diet seems to have acted like a shield for their developing brains, so preventing social and motivational problems from ever taking root.

“This matters because it suggests 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 a full‑blown pathologic condition.

“What’s more, we found that males and females benefited via different biological routes—males by reducing inflammation, females by boosting antioxidant defenses—hinting that we could personalize and refine such dietary interventions. 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 added, “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 which need to be better understood before we can apply this to humans.”

Commenting, Dr. Aniko Korosi, Associate Professor at the University of Amsterdam says, “This work nicely contributes further to the nascent 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. However, important questions remain in the field as to which nutrients, when, and for whom, are effective in modulating mental health.

“The presented study interestingly shows that prenatal stress‑induced risk of altered behavior can be modulated with a ketogenic diet fed after weaning. It will be intriguing to further explore what are the biological processes are involved in these beneficial effects and if such effects are sex-specific.”

This is an independent comment, Dr. Korosi was not involved in this work.