Consumption of a low-carbohydrate and high-fat diet (the ketogenic diet) exaggerates biotin deficiency in mice

Nutrition. 2013 Oct;29(10):1266-70. doi: 10.1016/j.nut.2013.04.011.


Objective: Biotin is a water-soluble vitamin that acts as a cofactor for several carboxylases. The ketogenic diet, a low-carbohydrate, high-fat diet, is used to treat drug-resistant epilepsy and promote weight loss. In Japan, the infant version of the ketogenic diet is known as the "ketone formula." However, as the special infant formulas used in Japan, including the ketone formula, do not contain sufficient amounts of biotin, biotin deficiency can develop in infants who consume the ketone formula. Therefore, the aim of this study was to evaluate the effects of the ketogenic diet on biotin status in mice.

Methods: Male mice (N = 32) were divided into the following groups: control diet group, biotin-deficient (BD) diet group, ketogenic control diet group, and ketogenic biotin-deficient (KBD) diet group. Eight mice were used in each group.

Results: At 9 wk, the typical symptoms of biotin deficiency such as hair loss and dermatitis had only developed in the KBD diet group. The total protein expression level of biotin-dependent carboxylases and the total tissue biotin content were significantly decreased in the KBD and BD diet groups. However, these changes were more severe in the KBD diet group.

Conclusion: These findings demonstrated that the ketogenic diet increases biotin bioavailability and consumption, and hence, promotes energy production by gluconeogenesis and branched-chain amino acid metabolism, which results in exaggerated biotin deficiency in biotin-deficient mice. Therefore, biotin supplementation is important for mice that consume the ketogenic diet. It is suggested that individuals that consume the ketogenic diet have an increased biotin requirement.

Keywords: Biotin; Biotin-dependent carboxylase; Hair loss and dermatitis; Ketogenic diet; Special infant formula.

MeSH terms

  • Amino Acids, Branched-Chain / metabolism
  • Animals
  • Biological Availability
  • Biotin / blood
  • Biotin / deficiency*
  • Biotin / pharmacokinetics
  • Biotinidase Deficiency / blood*
  • Biotinidase Deficiency / pathology
  • Blood Glucose / metabolism
  • Diet, Ketogenic / adverse effects*
  • Dietary Supplements
  • Gluconeogenesis / drug effects
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nutritional Status


  • Amino Acids, Branched-Chain
  • Blood Glucose
  • Biotin

Supplementary concepts

  • Biotin deficiency