Abstract
The ketogenic diet (KD) is a high-fat, moderate-protein, and low-carbohydrate diet. Initially prescribed for drug-resistant epilepsy, KD has become popular for weight reduction in patients with diabetes and obesity, who are often affected by reduced bone mass. However, KD’s impact on bone marrow cells remains largely unexplored. Here, we show the effects of low protein KD on bone marrow cells (BMCs) during pregnancy, lactation, and postnatal development in 30-day-old Wistar rat offspring. KD consumption in female juvenile rat offspring supported BMC osteogenic differentiation and inhibited osteoclast activity, while in male rat BMCs it reduced bone regenerative potential. This was observed despite a strongly reduced body weight in both sexes. The addition of the primary ketone body β-hydroxybutyrate (β-HB) to juvenile and adult rat BMC cultures in a low glucose culture medium effectively promoted extracellular matrix mineralization and proliferation of rat BMCs and reversed the negative impact of low glucose on BMC viability, inflammation, and osteoclast activity. Given the above, we recommend considering the potential sex differences when implementing restrictive diets and their consequences during pregnancy. Our results also highlight the distinct effects of low glucose and β-HB on the osteogenesis of juvenile and adult rat BMCs, which suggests caution in considering short-term KD or fasting for bone-related therapies.
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We would like to thank Wojciech Kosiek (Laboratory of Experimental Neuropathology) for providing photographs of rats raised on normal and ketogenic diets.
Funding
The research has been supported by Research Support Module ID.UJ grant no. U1U/W18/NO/28.63 (K.T.).
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K.T. experimental work, writing the manuscript, conceptualization, data verification, A.M.O. revising the manuscript, supervision, data verification, conceptualization, B.I. experimental work, Z.S. revising the manuscript and carrying out in vivo part. The authors have approved the final version of this article.
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Truchan, K., Ilnicki, B., Setkowicz, Z. et al. Ketogenic diet sex-dependent effects on rat bone marrow cells during development and β-HB protection in hypoglycemia. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40169-3
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DOI: https://doi.org/10.1038/s41598-026-40169-3
