Vitamin K2 Improves Anxiety and Depression but not Cognition in Rats with Metabolic Syndrome: a Role of Blood Glucose?

Folia Med (Plovdiv). 2016 Dec 1;58(4):264-272. doi: 10.1515/folmed-2016-0032.


Background: The metabolic syndrome is a socially important disorder of energy utilization and storage, recognized as a factor predisposing to the development of depression, anxiety and cognitive impairment in humans.

Aim: In the present study we examined the effects of vitamin K2 on the behavior of rats with metabolic syndrome and looked for relationships with the effects on blood sugar.

Materials and methods: Male Wistar rats were divided in four groups: a control group on a regular rat chow, a metabolic syndrome (MS) group fed a high-fat high-fructose diet, a control group treated with vitamin K2 and a MS group treated with vitamin K2. Vitamin K2 was given by gavage. At the end of the study (after 10 weeks) behavioral tests were performed and fasting blood glucose was measured. Anxiety was determined using the social interaction test and depression was assessed by the Porsolt test. Memory effects were estimated by the object recognition test. Correlations between fasting blood glucose and behavioral performance were analyzed.

Results: The rats from the MS group had elevated blood glucose. They had anxiety, depression and memory deficit. Vitamin K2 normalized blood glucose, reduced anxiety and depression, but did not improve memory. Time of social interaction (inverse index of anxiety) and memory recognition were negatively correlated with blood glucose in the untreated rats but the immobility time (measure of depression) was not. When vitamin K2-treated rats were added, the correlation of blood glucose with the time of social interaction was kept, but the one with the recognition memory was lost. It might be that the anxiolytic effect of vitamin K2 in this setting is at least partly due to its effects on blood glucose, while the anti-depressant effect is glucose-independent.

Conclusion: The present study demonstrated that vitamin K2 prevented the development of anxiety and depression, but did not improve the memory deficit caused by the dietary manipulation in an experimental model of metabolic syndrome. It might be that the anxiolytic effect of vitamin K2 is at least partly due to its effects on blood glucose, while the antidepressant effect is glucose-independent.

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Anxiety / psychology*
  • Behavior, Animal / drug effects*
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Cognition / drug effects*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / psychology*
  • Depression / metabolism
  • Depression / psychology*
  • Diet, High-Fat
  • Disease Models, Animal
  • Fructose
  • Male
  • Memory Disorders / metabolism
  • Memory Disorders / psychology
  • Memory, Short-Term
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / psychology*
  • Rats
  • Rats, Wistar
  • Social Behavior
  • Vitamin K 2 / pharmacology*
  • Vitamins / pharmacology*


  • Blood Glucose
  • Vitamins
  • Vitamin K 2
  • Fructose