Low-carbohydrate, high-fat diets have sex-specific effects on bone health in rats

Ayse Zengin, Benedikt Kropp, Yan Chevalier, Riia Junnila, Elahu Sustarsic, Nadja Herbach, Flaminia Fanelli, Marco Mezzullo, Stefan Milz, Martin Bidlingmaier, Maximilian Bielohuby

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15 Citations (Scopus)


Purpose: Studies in humans suggest that consumption of low-carbohydrate, high-fat diets (LC–HF) could be detrimental for growth and bone health. In young male rats, LC–HF diets negatively affect bone health by impairing the growth hormone/insulin-like growth factor axis (GH/IGF axis), while the effects in female rats remain unknown. Therefore, we investigated whether sex-specific effects of LC–HF diets on bone health exist.

Methods: Twelve-week-old male and female Wistar rats were isoenergetically pair-fed either a control diet (CD), “Atkins-style” protein-matched diet (LC–HF-1), or ketogenic low-protein diet (LC–HF-2) for 4 weeks. In females, microcomputed tomography and histomorphometry analyses were performed on the distal femur. Sex hormones were analysed with liquid chromatography–tandem mass spectrometry, and endocrine parameters including GH and IGF-I were measured by immunoassay. 

Results: Trabecular bone volume, serum IGF-I and the bone formation marker P1NP were lower in male rats fed both LC–HF diets versus CD. LC–HF diets did not impair bone health in female rats, with no change in trabecular or cortical bone volume nor in serum markers of bone turnover between CD versus both LC–HF diet groups. Pituitary GH secretion was lower in female rats fed LC–HF diet, with no difference in circulating IGF-I. Circulating sex hormone concentrations remained unchanged in male and female rats fed LC–HF diets. 

Conclusion: A 4-week consumption of LC–HF diets has sex-specific effects on bone health—with no effects in adult female rats yet negative effects in adult male rats. This response seems to be driven by a sex-specific effect of LC–HF diets on the GH/IGF system.

Original languageEnglish
Pages (from-to)2307 - 2320
Number of pages14
JournalEuropean Journal of Nutrition
Issue number7
Publication statusPublished - 2016
Externally publishedYes


  • Bone mineral density
  • Growth hormone
  • Insulin-like growth factor-I
  • Ketogenic diet
  • Nutrition
  • Sex hormones

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