Research & Education

Vitamin K2 – The Missing Link in Osteoporosis?

Research in the last few decades has highlighted the positive effect of vitamin K, a fat-soluble vitamin, on bone health and strength. Increasing evidence concludes that suboptimal vitamin K status or low vitamin K consumption is associated with an increased risk of fracture, lower bone mass, and increased bone turnover. More specifically, there may be a link between vitamin K insufficiency and osteoporosis, as low circulating vitamin K concentrations have been found in patients with osteoporosis. 

Three Types of Vitamin K 

There are three known types of vitamin K: K1, K2, and K3. Among the three, vitamin K2, or menaquinone, has been shown to promote bone strength and health. K2 is synthesized by intestinal flora and can be found in fermented foods like natto (fermented soybeans), dairy products, egg yolks, liver, and meat. The most common type of K2 is menaquinone-4 (MK-4). Currently, there is no recommended daily intake (RDI) set for K2 because vitamin K2 is endogenously produced in the human body from K1 and a precursor called geranylgeranyl (GG)

Some research suggests that dietary intake of vitamin K, in general, may not be sufficient for optimal status and may need to be complemented by K1 or K2 supplementation. However, supplementing with just K1 alone may not be sufficient to support bone health, as the conversion of K1 to K2 can be suboptimal. Thus, K2 and GG may be considered conditionally essential, and supplementation of these nutrients may be recommended for certain individuals. 

Roles of Vitamin K2 in Bone Health 

The most direct way vitamin K promotes bone health is through three vitamin K-dependent proteins in bone and cartilage: osteocalcin, matrix γ-carboxyglutamic acid protein, and protein S. Osteocalcin is a recognized marker of bone formation. Without vitamin K, an essential cofactor for enzymatic carboxylation, osteocalcin lacks structural integrity and cannot bind to hydroxyapatite.

Other bone-supportive roles of vitamin K include upregulating the transcription of osteoblastic (bone-building) markers, the formation of osteoclasts, and bone resorption. It may also stimulate osteoblast genesis in bone marrow cells and help reduce osteoblast apoptosis. Moreover, vitamin K2 (MK-4) has been shown to help stimulate collagen synthesis in vitro. This might help explain how K2 supports healthy arterial elasticity and is partially responsible for increased bone strength. The collagen content of bone is believed to influence bone strength, elasticity, and fracture risk. 

Clinical Research of Vitamin K2 for Bone Health 

Extensive clinical trials have delved into the potential benefits of vitamin K2 for bone health, especially for postmenopausal women with osteoporosis. Researchers have demonstrated that patients with osteoporosis who received vitamin K2 supplementation, either alone (n = 241) or combined with calcium (n = 63) or vitamin D3 (n = 172), exhibited increased bone mineral density (BMD), increased stimulation of bone formation and resorption activity, and a significant decrease in undercarboxylated osteocalcin. These trials observed positive outcomes following the administration of 45 mg/day of vitamin K2 for one to two years. In contrast, one study observed that even a low daily intake of just 1.5 mg/day of K2 for one year helped promote bone quality. 

In a randomized controlled trial conducted by Yonemura et al. (n = 60), it was concluded that combining vitamin K2 and D3 may offer support to men and women on prednisolone, a medication associated with increased BMD loss. Lastly, a systematic review and meta-analysis of thirteen trials by Cockayne et al. suggested that patients receiving K1 and K2 supplementation, particularly MK-4, exhibited increased BMD and approximately an 80% risk reduction of hip fractures

Clinical Insights 

Postmenopausal women are at an increased risk of developing osteoporosis and fractures of the spine and hip. Osteoporotic hip fractures are associated with a significant increase in mortality (15% to 20%), particularly in older adults. While osteoporosis's development is multifactorial, the role of vitamin K2 insufficiency is emerging. Due to its role in bone strength and remodeling factors, supporting vitamin K2 through dietary and supplemental intake may be clinically beneficial to those seeking bone support. 

By Danielle Moyer Male, MS, CNS, LDN