Vitamin K2 Alleviates Insulin Resistance in Skeletal Muscle by Improving Mitochondrial Function via SIRT1 Signaling (Su X et al.)

Antioxidants & Redox Signaling journal has recently published results of a study that aimed to investigate the hypothesis that vitamin K2’s alleviation of insulin resistance (IR) and improvement of insulin sensitivity may be due to activation of the SIRT1 signaling pathway. For the purpose of this study the researchers have tested vitamin K2’s modulation of mitochondrial function to protect against IR by SIRT1 in high-fat diet (HFD)-fed mice and palmitate acid (PA)-exposed C2C12 cell models and established that vitamin K2 supplementation could effectively ameliorate the development of IR by improving mitochondrial function in vivo and in vitro.

High-fat diet (HFD)-induced IR impairs skeletal muscle mitochondrial biogenesis and functions, adversely affecting human health and lifespan. At present, vitamin K2 is approved as an anti-osteoporotic medicine in Asia, and apart from anticoagulant effect of warfarin, vitamin K2 does not cause any serious side effects regardless of its dose. Recently, researchers found that vitamin K2 has a beneficial role in improving insulin sensitivity and glucose metabolism through the involvement of VK-dependent protein osteocalcin, anti-inflammatory properties, and lipid-lowering effects. Otherwise, vitamin K2’s alleviation of IR is also associated with an increasing level of serum adiponectin, an adipocyte-secreted hormone that acts as an insulin sensitizer. However, the mechanisms underlying vitamin K2’s effect on insulin sensitivity were still unclear. The authors of this study revealed a previously undiscovered mechanism by which HFD-caused mitochondrial dysfunction could be reversed by vitamin K2 treatment. Vitamin K2 enhanced the mitochondrial function by improving mitochondrial respiratory capacity, increasing mitochondrial biogenesis and the enzymatic activities of mitochondrial complexes through SIRT1 signaling. Vitamin K2 triggers the SIRT1 signaling pathway, resulting in SIRT3 enrichment within mitochondria and increasing mitochondrial antioxidant protein manganese superoxide dismutase (SOD2) deacetylation and decreasing mitochondrial reactive oxygen species production. Furthermore, vitamin K2 had beneficial effects on increasing the proportion of oxidative fibers in skeletal muscle and alleviating saturated fatty acid concentrations via SIRT1 in HFD-fed mice. The authors concluded that “SIRT1 has a master role in the protective effect of VK2 on IR in vivo and in vitro”, and their results also suggest that vitamin K2 may be a therapeutic target for the amelioration of IR.

“This research for the first time proposed a potential mechanism underlying the amelioration of IR by vitamin K2 mediated through SIRT1,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “Given the intense clinical interest in developing novel preventive and therapeutic strategies that can mitigate both insulin resistance and the consequences of mitochondrial dysfunction, this findings that vitamin K2 has both of these functions indicate that it could have significant potential for development as a novel pharmacological agent to improve IR,” she emphasizes.


Su X, Wang W, Fang C, et al. Vitamin K2 alleviates insulin resistance in skeletal muscle by improving mitochondrial function via SIRT1 signaling [published online ahead of print, 2020 Apr 7]. Antioxid Redox Signal. 2020;10.1089/ars.2019.7908. doi:10.1089/ars.2019.7908


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