Science Update

Vitamin K2 and GG Mitigate Insulin Resistance by Improving Mitochondrial Function

Vitamin K2, or menaquinone, is a versatile vitamin complex that is well-known for its role in supporting arterial and bone health. More recent research suggests it may have a potential role in the treatment of certain autoimmune conditions and mitochondrial dysfunction. Research suggests that mitochondrial dysfunction within skeletal muscle may be a possible contributor to type 2 diabetes due to reduced mitochondrial biogenesis in those populations.

According to a recent article published last month in Antioxidants & Redox Signaling, vitamin K2 (VK2) can reverse high-fat diet (HFD)-induced mitochondrial dysfunction in mice and cell models. Researchers investigated the underlying mechanisms of VK2 supplementation on insulin sensitivity and mitochondrial function. They were surprised to find that in HFD-fed mice and palmitic acid (PA)-exposed cells, VK2 supplementation “could effectively ameliorate the development of insulin resistance by improving mitochondrial function.”

The mechanisms by which insulin resistance was alleviated by NK2 treatment in skeletal muscle was tested in HFD-fed mice and PA-exposed cells. The results of the study showed a decrease in surtuin 1 (SIRT1) expression — the key regulator of energy metabolism — and an increase in the production of mitochondrial reactive oxygen species (ROS) when mice were fed a high-fat diet and cells were exposed to PA. This ultimately resulted in mitochondrial dysfunction and increased insulin resistance. However, when the mice and cell models were treated with VK2, SIRT1 signaling and PGC-1α expression activity was upregulated, increasing mitochondrial biogenesis and enzyme activity within the mitochondrial respiratory chain complex.

Moreover, researchers investigated the effects of geranylgeraniol (GG) on mitochondrial function and SIRT1-protein expression in PA-exposed cells and found that it improved mitochondrial membrane potential and adenosine triphosphate (ATP) production. Both VK2 and GG — the side chain structure of vitamin K2 — also significantly improved mitochondrial respiratory capacity. VK2 treatment was also shown to increase mitochondrial ROS–scavenging capacity by stimulating SIRT3 expression and improving free fatty acid concentrations by upregulating PPAR-α expression, which have been shown to have a protective effect on insulin resistance.

This research has uncovered new mechanisms in which vitamin K2 (with the support of GG) contributes to the inhibition of insulin resistance in skeletal muscle through SIRT1 signaling activation. Although human clinical trials are needed to better understand this phenomenon for clinical application, these results suggest that vitamin K2 (along with GG) supplementation may be a potential option for helping to support the management of insulin sensitivity in patients with insulin resistance. Considering dietary vitamin K2 intake is insufficient in the standard American diet or in Western pattern diets, supplementation may not only support mitochondrial and musculoskeletal health, but it may also contribute to healthy blood sugar regulation.

By Caitlin Higgins, CNS, LDN, MS