Ketogenic diet impairs neurological development of neonatal rats and affects biochemical composition of maternal brains: evidence of functional recovery in pups

Abstract

The ketogenic diet (KD) is a type of diet in which the intake of fats significantly increases at the cost of carbohydrates while maintaining an adequate amount of proteins. This kind of diet has been successfully used in clinical therapies of drug-resistant epilepsy, but there is still insufficient evidence on its safety when used in pregnancy. To assess KD effects on the course of gestation and fetal development, pregnant females were fed with: (i) KD during pregnancy and lactation periods (KD group), (ii) KD during pregnancy replaced with ND from the day 2 postpartum (KDND group) and (iii) normal diet alone (ND group). The body mass, ketone and glucose blood levels, and food intake were monitored. In brains of KD-fed females, FTIR biochemical analyses revealed increased concentrations of lipids and ketone groups containing molecules. In offspring of these females, significant reduction of the body mass and delays in neurological development were detected. However, replacement of KD with ND in these females at the beginning of lactation period led to regainment of the body mass in their pups as early as on the postnatal day 14. Moreover, the vast majority of our neurological tests detected functional recovery up to the normal level. It could be concluded that the ketogenic diet undoubtedly affects the brain of pregnant females and impairs the somatic and neurological development of their offspring. However, early postnatal withdrawal of this diet may initiate compensatory processes and considerable functional restitution of the nervous system based on still unrecognized mechanisms.

Does Ketogenic Diet Used in Pregnancy Affect the Nervous System Development in Offspring?─FTIR Microspectroscopy Study

“…It is also worth mentioning here, that at the beginning of postnatal life, the offspring of mothers fed with KD during pregnancy had significantly lower body mass what was described in details in our previous work . When, on the 2nd day postpartum, in KD-fed mothers, normal diet was introduced, and their progeny began to rebuilt the body mass very quickly.…”

“…The immature brain is able to take up KB from two to three times more efficiently than the mature one and use them for energy metabolism and lipid as well amino acid biosynthesis. ,− Our earlier study carried out on adults male Wistar rats showed increased intensity of the band at 1740 cm –1 in hippocampal formation of animals fed with KD . On the other hand, we did not notice an elevated level of this band in the females fed with KD 2 days postpartum, although the level of β-hydroxybutyrate in their blood was significantly higher both on the day of fertilization as well as on 4th, 15th, and 20th gestational day …”

“…KD is a high-fat and low-carbohydrate diet that goal is to imitate a beneficial effects of fasting but without depriving the organism calories demanded to metabolism. , During KD, fat intake should be around 80% of total caloric consumption, thus changing the main energy source for metabolism from carbohydrates to fats and inducing ketone body production in the liver. ,, Acetoacetate, which spontaneously converts into acetone, and β-hydroxybutyrate are the ketone bodies (KBs) produced from fatty acids in the liver which during KD become the major source of energy for the central nervous system, replacing glucose. , KBs are able to cross the blood–brain barrier through monocarboxylate transporters (MCTs) of endothelial cells and astroglia . However, the mechanism of KD action in patients with drug-resistant epilepsy is not fully understood .…”

“…4,8 During KD, fat intake should be around 80% of total caloric consumption, thus changing the main energy source for metabolism from carbohydrates to fats and inducing ketone body production in the liver. 4,9,10 Acetoacetate, which spontaneously converts into acetone, and β-hydroxybutyrate are the ketone bodies (KBs) produced from fatty acids in the liver which during KD become the major source of energy for the central nervous system, replacing glucose. 4,10 KBs are able to cross the blood− brain barrier through monocarboxylate transporters (MCTs) of endothelial cells and astroglia.…”

“…4,9,10 Acetoacetate, which spontaneously converts into acetone, and β-hydroxybutyrate are the ketone bodies (KBs) produced from fatty acids in the liver which during KD become the major source of energy for the central nervous system, replacing glucose. 4,10 KBs are able to cross the blood− brain barrier through monocarboxylate transporters (MCTs) of endothelial cells and astroglia. 11 However, the mechanism of KD action in patients with drug-resistant epilepsy is not fully understood.…”