Vitamin K, especially K2, improves bone health by enhancing carboxylation of osteocalcin (cOC) – a process that binds calcium into bones – according to researchers from Qingdao University’s School of Public Health, China.
The research was funded by Shandong Provincial Nature Foundation and Nature Foundation of Qingdao City.
The findings revealed that vitamin K supplementation significantly increased bone mineral density by increasing cOC and reducing uncarboxylated osteocalcin (ucOC).
The right balance between cOC and ucOC is important as high levels of ucOC may indicate insufficient vitamin K levels, leading to suboptimal calcium integration into bones and potentially weaker bones.
However, vitamin K had no significant impact on total levels of osteocalcin – a protein produced by bone-forming cells that binds calcium and integrates it into the bone matrix, helping to strengthen bones.
“This review suggests that the beneficial effects of vitamin K supplementation on bone health primarily involve enhancing the carboxylation of osteocalcin rather than altering the total amount of osteocalcin,” wrote researchers in Bone & Joint Research.
The benefits of vitamin K supplementation were also found to be more pronounced in women.
“Subgroup analysis revealed that vitamin K notably enhanced bone health in females by increasing lumbar spine bone mineral density and decreasing ucOC. Vitamin K, especially vitamin K2, exhibited effects on maintaining or increasing lumbar spine BMD, and influencing the balance of cOC and ucOC,” said researchers.
These findings are significant for prevention and management of bone-related diseases, especially in the context of global population ageing.
Managing bone health
The worldwide prevalence of osteoporosis and osteoarthritis is estimated to affect approximately 200 million and 527 million patients, respectively. Furthermore, studies indicate a fracture risk of one in three women and one in five men.
Previous research suggested that vitamin K plays a significant role in bone health. Vitamin K facilitates cOC, which is essential for bone metabolism – a continuous process essential for maintaining bone structural integrity and mineral balance throughout life.
Vitamin K is a fat-soluble nutrient that exists in two primary forms: vitamin K1, which is predominantly found in green vegetables, vegetable oils, or fruits; and vitamin K2, which is present in animal and fermented foods and is synthesised by gut bacteria.
The main supplementation forms of vitamin K2 are MK-7 and MK-4.
Vitamin K is crucial in the carboxylation process of osteocalcin, which is initially in its uncarboxylated form (uncarboxylated osteocalcin or ucOC), converting it into cOC. This is required for bone mineralisation and overall bone health.
Researchers therefore wanted to explore the effects of vitamin K through dietary interventions, which could improve bone health among older populations.
Effects of vitamin K supplementation on bone health
Researchers reviewed 17 RCTs in regions including China, Australia, South Korea, Japan, and Indonesia.
There was a total of 4,800 male and female subjects with mean ages of 47 to 75.8 years old. They included healthy adults and patients diagnosed with osteoporosis or osteopenia.
The objectives were to examine the effects of vitamin K supplementation on bone mineral density in middle-aged and older adults, and to identify bone markers affected by vitamin K.
Researchers found that vitamin K, especially vitamin K2, maintains or increases lumbar spine bone mineral density in middle-aged and elderly people. Overall, vitamin K supplementation led to significant improvement of bone density in the lower spine, with an increase of 0.01 g/cm², although the results showed considerable variation, said researchers.
Additionally, vitamin K2 supplementation showed a similar significant increase in lumbar spine bone mineral density of 0.02 g/cm². This effect was more pronounced than Vitamin K1 supplementation, which did not yield any significant changes in BMD at 0.00 g/cm².
Subgroup analysis also revealed that vitamin K supplementation effects were most notable in women, who showed a bone mineral density increase of 0.01 g/cm².
In contrast, studies involving both sexes did not show a significant effect, with a change of 0.00 g/cm².
These results highlight the differential impacts of vitamin K forms and demographic factors on lumbar spine bone health.
Increasing conversion of ucOC to cOC improves bone health
The observed effects of vitamin K are achieved mainly through increasing the conversion of ucOC to cOC, according to researchers. This is reflected in the results, which indicated significantly increased levels of cOC by 2.87 ng/ml. At the same time, it significantly reduced levels of ucOC by 2.32 ng/ml.
Vitamin K supplementation also improved the balance between cOC and ucOC, with the ratio of cOC to ucOC increasing by 1.98 and the ratio of ucOC to tOC decreasing by 0.21.
These findings underscore vitamin K’s role in enhancing the carboxylation process, which is essential for bone health.
However, vitamin K supplementation did not have a significant effect on total osteocalcin (tOC), showing an increase of just 1.13 ng/ml. There was also no significant effect of vitamin K supplementation on other bone metabolism markers, such as cross-linked telopeptide of type 1 collagen (which measures bone breakdown), bone alkaline phosphatase (a marker of bone formation), and procollagen I N-terminal propeptide (which reflects collagen production in bones).
This was inconsistent with previous studies, which is likely due to the small number of studies included or the control groups’ use of calcium and vitamin D that could mask the effects of vitamin K.
These results further indicated that vitamin K supplementation primarily affects bone health through carboxylation of osteocalcin, with minimal impact on other bone metabolism markers.
“The fact that only osteocalcin-related biomarkers changed suggests that we may need to consider the combined use of other bone nutrients. Further research is needed to fully understand the mechanisms by which vitamin K affects bone metabolism,” said researchers, adding that dietary patterns significantly impact osteoporosis prevention and fracture recovery.
Researchers recommend enhancing public health campaigns to increase awareness regarding the significance of vitamin K2.
“In addition, we advise older adults, especially postmenopausal women, to consider the proper use of vitamin K supplements or to boost their consumption of green leafy vegetables and fermented foods.
“Lastly, we propose the development of personalised nutrition plans to optimise nutrient supplementation,” researchers concluded.
