Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan.

Low-carbohydrate, high-fat ketogenic diets (KDs) are used for treating drug-resistant epilepsy, and other potential benefits, such as treating neurological disorders, metabolic syndrome, and cancer are being explored. In addition to these and other medical applications, KDs have also become popular...

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Main Authors: Sarah M Zala, Renata Santos, Eva Strasser, Alice Schadde, Sarah Kugler, Verena Strauss, Anna Kübber-Heiss, Diana Zala
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0328455
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author Sarah M Zala
Renata Santos
Eva Strasser
Alice Schadde
Sarah Kugler
Verena Strauss
Anna Kübber-Heiss
Diana Zala
author_facet Sarah M Zala
Renata Santos
Eva Strasser
Alice Schadde
Sarah Kugler
Verena Strauss
Anna Kübber-Heiss
Diana Zala
author_sort Sarah M Zala
collection DOAJ
description Low-carbohydrate, high-fat ketogenic diets (KDs) are used for treating drug-resistant epilepsy, and other potential benefits, such as treating neurological disorders, metabolic syndrome, and cancer are being explored. In addition to these and other medical applications, KDs have also become popular for rapid weight-loss and enhancing athletic performance. However, the potential negative effects of exposing developing offspring to KDs during pregnancy (gestational KD) are poorly understood, and especially the long-term health consequences. In this study, we investigated the effects of a partial gestational KD administered during the second half of pregnancy and assessed the consequences on the offspring over their entire lifespan. We found that, compared to controls, a gestational KD significantly reduced dams' litter size and litter mass and altered the litter sex ratio, reducing the proportion of female offspring, which also had lower body mass early in their life. In contrast, male offspring exposed to a gestational KD suffered a significantly reduced lifespan and a late-onset increase in body mass. We found no evidence that a KD diet influenced some adult offspring behaviors (locomotion, anxiety, depression, circadian rhythms, food and water consumption) or reproductive success. Our results with laboratory mice may not translate to human health, but nevertheless, they should raise concerns that even a partial maternal KD during pregnancy may have detrimental effects on offspring health and longevity.
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spelling doaj-art-bfaae4775bc0450ebed9fa55e83d3a792025-08-20T03:12:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01207e032845510.1371/journal.pone.0328455Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan.Sarah M ZalaRenata SantosEva StrasserAlice SchaddeSarah KuglerVerena StraussAnna Kübber-HeissDiana ZalaLow-carbohydrate, high-fat ketogenic diets (KDs) are used for treating drug-resistant epilepsy, and other potential benefits, such as treating neurological disorders, metabolic syndrome, and cancer are being explored. In addition to these and other medical applications, KDs have also become popular for rapid weight-loss and enhancing athletic performance. However, the potential negative effects of exposing developing offspring to KDs during pregnancy (gestational KD) are poorly understood, and especially the long-term health consequences. In this study, we investigated the effects of a partial gestational KD administered during the second half of pregnancy and assessed the consequences on the offspring over their entire lifespan. We found that, compared to controls, a gestational KD significantly reduced dams' litter size and litter mass and altered the litter sex ratio, reducing the proportion of female offspring, which also had lower body mass early in their life. In contrast, male offspring exposed to a gestational KD suffered a significantly reduced lifespan and a late-onset increase in body mass. We found no evidence that a KD diet influenced some adult offspring behaviors (locomotion, anxiety, depression, circadian rhythms, food and water consumption) or reproductive success. Our results with laboratory mice may not translate to human health, but nevertheless, they should raise concerns that even a partial maternal KD during pregnancy may have detrimental effects on offspring health and longevity.https://doi.org/10.1371/journal.pone.0328455
spellingShingle Sarah M Zala
Renata Santos
Eva Strasser
Alice Schadde
Sarah Kugler
Verena Strauss
Anna Kübber-Heiss
Diana Zala
Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan.
PLoS ONE
title Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan.
title_full Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan.
title_fullStr Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan.
title_full_unstemmed Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan.
title_short Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan.
title_sort sex dependent effects of a gestational ketogenic diet on offspring birth and lifespan
url https://doi.org/10.1371/journal.pone.0328455
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