A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice

Exp Neurol. 2018 Aug:306:149-157. doi: 10.1016/j.expneurol.2018.05.011. Epub 2018 May 17.


Current experiments investigated whether a ketogenic diet impacts neuropathy associated with obesity and prediabetes. Mice challenged with a ketogenic diet were compared to mice fed a high-fat diet or a high-fat diet plus exercise. Additionally, an intervention switching to a ketogenic diet following 8 weeks of high-fat diet was performed to compare how a control diet, exercise, or a ketogenic diet affects metabolic syndrome-induced neural complications. When challenged with a ketogenic diet, mice had reduced bodyweight and fat mass compared to high-fat-fed mice, and were similar to exercised, high-fat-fed mice. High-fat-fed, exercised and ketogenic-fed mice had mildly elevated blood glucose; conversely, ketogenic diet-fed mice were unique in having reduced serum insulin levels. Ketogenic diet-fed mice never developed mechanical allodynia contrary to mice fed a high-fat diet. Ketogenic diet fed mice also had increased epidermal axon density compared all other groups. When a ketogenic diet was used as an intervention, a ketogenic diet was unable to reverse high-fat fed-induced metabolic changes but was able to significantly reverse a high-fat diet-induced mechanical allodynia. As an intervention, a ketogenic diet also increased epidermal axon density. In vitro studies revealed increased neurite outgrowth in sensory neurons from mice fed a ketogenic diet and in neurons from normal diet-fed mice given ketone bodies in the culture medium. These results suggest a ketogenic diet can prevent certain complications of prediabetes and provides significant benefits to peripheral axons and sensory dysfunction.

Keywords: DRG; Diabetes; Exercise; High-fat; Ketogenic; Ketones; Mice; Pain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity
  • Animals
  • Axons / pathology
  • Blood Glucose / metabolism
  • Diet, High-Fat
  • Diet, Ketogenic*
  • Hyperalgesia / diet therapy*
  • Hyperalgesia / etiology*
  • Insulin / blood
  • Male
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / diet therapy*
  • Metabolic Syndrome / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neurites
  • Peripheral Nerves / growth & development*
  • Peripheral Nerves / pathology
  • Physical Conditioning, Animal
  • Weight Loss


  • Blood Glucose
  • Insulin