Vitamin K consists of a group of lipophilic, hydrophobic vitamins, such as Vitamins K1, K2, K3, K4 and K5. Among these, Vitamin K1 and K2 are the most important vitamins. Vitamin K2, also referred as menaquinone, has a varying length of side chain with repeating prenyl units. Based on the number of repeating prenyl units, Vitamin K2 is further classified as MK-2 to MK-14. Vitamin K2 is primarily produced by bacteria, such as Escherichia coli (which can produce the menaquinones MK-7 to MK-11), in the gut. It is also found in small amounts in in meat, dairy, eggs, and fermented foods, such as cheese, yogurt, and natto. Vitamin K2 accounts for about 10–25%, in a Western diet. Of the vitamin K2 absorbed, MK-4 accounts for about 30–40%.
Impact of Vitamin K2 on Bone Health
The human skeleton is replaced every seven to ten years. The skeleton’s remodelling is regulated by osteoblasts cells (which build up the skeleton), and osteoclasts cells (which break down the skeleton). Osteoblasts produce osteocalcin, which influences bone mineralization through its ability to bind to the mineral component of bone, hydroxyapatite, which in turn makes the skeleton stronger and less susceptible to fracture. Vitamin K2 is required to activate the newly made osteocalcin, so that it would be able to bind calcium. Vitamin K2 along with Vitamin D3 inhibit the action of osteoclasts, thereby reducing loss of bone mass. Thus, Vitamin K2 plays a key role in improving bone health.
Impact of Vitamin K2 on Human Health
Other than its impact on bone health, Vitamin K2 is also associated with the inhibition of arterial calcification and arterial stiffening, thereby lowering the risk of vascular damage. Thus, an increased intake of Vitamin K2 can help in lowering calcium associated health risks.
Moreover, Vitamin K2 also helps in ensuring healthy skin, promoting brain function, supporting growth and development, and preventing cancer.
“Osteoporosis is defined as a metabolic bone disease characterised by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk.” The prevalence of osteoporosis-related fractures increases rapidly with age. According to various studies, it increases from 4% in women at age 50-59 to 52% in women aged more than 80 years. Worldwide, it is believed that 1 in 3 women and 1 in 5 men over the age of 50 years are expected to experience an osteoporotic fracture.”
Research from randomized controlled trial of female patients with osteoporosis showed significant increase in the BMD of the test subjects when supplemented with Vitamin K2. This provided evidence that the risk of osteoporotic fracture can be reduced through Vitamin K2 supplements.
Importance of Vitamin K2 for Prevention of Osteoporosis
Vitamin K deficiency, as indicated by an increased circulating level of undercarboxylated osteocalcin, may contribute to osteoporotic fractures. According to a report of the World Health Organization (WHO) Vitamin K2, which stimulates bone formation via gamma-carboxylation of osteocalcin and/or steroid and xenobiotic receptors (SXRs), reduces the incidence of vertebral fractures, despite having only modest effects on the bone mineral density (BMD). Thus, Vitamin K2, which helps in improving lumbar bone mineral density, can play a significant role in preventing osteoporotic fractures in patients with age-related osteoporosis, glucocorticoid-induced osteoporosis, or liver-dysfunction-induced osteoporosis. A systematic review of Japanese patients has shown that Vitamin K2 can help in preventing vertebra fractures by 60%, hip fractures by 77%, and nonvertebral fractures by 81%.
Use of Vitamin K2 for Treatment of Osteoporosis
Even though the effect of Vitamin K2 on the BMD is quite modest, it has potential to regulate bone metabolism and play a key role in reducing the risk of osteoporotic fractures. In Japan, it has been well established that Vitamin K2 enhances gamma-carboxylation of bone glutamic acid residues and secretion of osteocalcin, sustains lumbar BMD, and thereby prevents osteoporotic. Since 1995, Vitamin K2 has been approved for the treatment of osteoporosis in Japan. Menatetrenone (MK-4), a form of Vitamin K2, along with raloxifene, and bisphosphonates (such as etidronate, alendronate, and risedronate), are widely used in the treatment of postmenopausal osteoporosis. Studies in Japan have highlighted that supplementing vitamin K2 at 180 μgm/day can reduce the usual age related decline in BMD in the lumbar spine and femoral neck but not the total hip.
The Ministry of Health, Labour, and Welfare in Japan has approved, Menatetrenone, a synthetic Vitamin K2, which is chemically identical to menaquinone-4, as an anti-osteoporotic medicine.
Role of Vitamin K2 on Reversal of Osteoporosis
Vitamin K2 supports bone formation and suppresses bone resorption by stimulating the expression of cytokines such as osteoprotegerin (OPG) and inhibiting the expression of receptor activator of nuclear factor kappa-B ligand on osteoblasts/ osteoclasts. It improves the function of osteoblasts by inducing their proliferation, decreasing their apoptosis, and increasing the expression of osteogenic genes. It also has positive effects on the bone turnover and regulates bone metabolism. Thus, Vitamin K2 with its inhibitory effect on osteoclastic bone resorption, may be considered for avoiding osteoporosis or reversal of its impact by improving bone health.
Vitamin K2 is widely used in Japan for prevention and treatment of osteoporosis. Western countries, such as the United States and Canada, however, do not recommend use of Vitamin K2 for osteoporosis. Until there are significant studies to support taking Vitamin K2 supplements, the focus shall be on getting balanced diet to ensure availability of Vitamin K2 to maintain healthy bones.