Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food Funct. 2020 Apr;11(4):3280-3297.

Bone-related diseases such as osteoporosis are on the rise, due to an aging population, and are particularly common in post-menopausal women. Nutrition is known to play a vital role in the prevention and treatment of bone diseases. Vitamin D is well-studied in the prevention and treatment of osteoporosis and osteopenia, either given alone or in combination with calcium. Vitamin D regulates calcium metabolism, and stimulates bone matrix formation and maturation. Additionally, an increasing number of studies are highlighting the beneficial effects of vitamin K on bone health. Vitamin K is involved in calcium utilisation within the body, and promotes the integration of calcium into bone. Due to their complementary actions on calcium homeostasis and bone formation, combined supplementation of vitamin D and Vitamin K may be most beneficial.

A meta-analysis investigated the effects of vitamin D plus vitamin K on bone mineral density. Eight randomised controlled trials involving 971 participants were included in the analysis. The participants were primarily women, between the ages of three and eighty years. All of the included studies were of reasonable duration, between six months and three years. The dose of vitamin D used was 10 µg (400 IU) daily in all studies except one, which used 1 µg (40 IU) per day. Doses of vitamin K ranged widely, from 100 µg per day to 45 mg per day. The results showed that the combined supplementation of vitamin D and vitamin K significantly increased total bone mineral density, with a pooled effect size of 0.316, indicating a moderate effect size (p=0.03). Subgroup analysis showed that these effects were greater when only women were included (pooled effect size 0.41, p=0.019), and when vitamin K2 was used, rather than vitamin K1 (pooled effect size 0.57, p=0.03). Furthermore, the analysis found that combined supplementation significantly reduced levels of undercarboxylated osteocalcin (p<0.001). Osteocalcin is a calcium-binding protein found in bone which is involved in bone mineralisation. In order to be activated, osteocalcin must be carboxylated by vitamin K. Therefore, a decrease in undercarboxylated osteocalcin, as seen in this meta-analysis, indicates that there is more active osteocalcin present, thanks to adequate vitamin K levels. This may explain the mechanism of vitamin K supplementation’s beneficial effects on bone mineral density. Comparison with other published meta-analyses suggests that combined supplementation of vitamin D and vitamin K may be more beneficial than supplementation with either vitamin alone.

This meta-analysis provides strong support for the benefits of combined vitamin D and vitamin K for bone health.