About Vitamin K2
Centuries ago in feudal Japan, Samurai warriors used to consume large amounts of natto - a dish made of fermented soybeans. Even today, it is consumed widely and considered as the highest food source of vitamin K2. Besides natto, Vitamin K2 can also be found in many fermented foods, such as miso and sauerkraut, as well as in animal products, including meat, butter, egg yolks, cheese, and yogurt. Historically, human diets were rich in vitamin K2, but at some point, this changed and now many people suffer from a deficiency of this vitamin.
Scientific research suggests that modern Western diets are not providing sufficient amounts of vitamin K2, which is an essential nutrient. This deficiency has become a common problem among people in recent times, even though human diets were abundant in vitamin K2 in the past.
What is vitamin K2?
Vitamin K2 is an essential nutrient required by the body throughout our lives. This fat-soluble vitamin helps activate calcium-binding proteins, which aid in the efficient distribution of Calcium to necessary places and contribute to bone health. It also plays a crucial role in blood clotting, which accelerates the healing process of wounds.
There are two forms of Vitamin K2, synthetic MK-4, and natural MK-7. Natural MK-7 is more readily absorbed by the body than synthetic MK-4, as suggested by studies. MenaQ7 is a vegan-friendly and allergen-free form of Vitamin K2, which is known to be the most bioactive form of Vitamin K2 available in the market. It has been used in various clinical trials to explore the potential benefits of this little-known vitamin.
Studies
Study 1 - Decreased Levels of Circulating Carboxylated Osteocalcin in Children with Low Energy Fractures: A Pilot Study
Study details
- Group 1: 20 children (6 girls and 14 boys) aged 5 to 15 years old, with radiologically confirmed low-energy fractures
- Group 2: 19 healthy children (10 girls and 9 boys) aged 7 to 17 years old, with no fractures
- Total vitamin D (25(OH)D3 plus 25(OH)D2), Calcium, BALP (bone alkaline phosphatase), NTX (N-terminal telopeptide), and uncarboxylated (ucOC) and carboxylated osteocalcin (cOC) serum concentrations were evaluated.
- The ratio of serum uncarboxylated osteocalcin to serum carboxylated osteocalcin (UCR) was used to indicate bone vitamin K status.
Results
There were no notable statistical variances observed in the serum calcium, NTx, BALP, or total vitamin D levels between the two groups. Nevertheless, a significant difference was identified in the UCR ratio. The median UCR value in the fracture group stood at 0.471, higher than the control group's value of 0.245 (p < 0.0001). Through logistic regression analysis, it was determined that the odds ratio for low-energy fractures associated with UCR exhibited a substantial increase, approximately 78.3 times higher.
Conclusions
A superior vitamin K status, indicated by the ucOC:cOC-UCR ratio, demonstrates a positive and statistically significant correlation with a decreased incidence of low-energy fractures.
Study 2 - Vitamin K Supplementation Modulates Bone Metabolism and Ultra-Structure of Ovariectomized Mice
Study details
- 24 female mice, aged 6 months old
- Divided into 4 groups, including SHAM Operated MOCK Treated, SHAM Operated VK Treated, OVX MOCK Treated, and OVX VK Treated
- Duration: 90 days
Measurements
- Researchers employed various techniques, including DXA, µCTScan, and SEM, along with biomolecular methods, like ELISA and qRT-PCR, to determine the effects of chronic VK usage on bone structure and mineral metabolism in OVX mice.
- A comprehensive analysis of serum hormonal levels and other molecules linked to bone and lipid metabolism was conducted to gain insight into the effects of VK in a menopausal murine model.
Results
- VK treatment has a significant impact on Pi metabolism regardless of OVX, resulting in alterations in plasma Pi levels, urinary output, balance, and Pi content in bone. Intriguingly, VK administration also led to an increase in VLDL levels in mice independently of castration.
- VK was found to enhance compact bone mass in OVX mice, as evidenced by assessments using DXA, histomorphometry, and µCT scanning. This was accompanied by elevated levels of bone formation markers, such as osteocalcin, HYP-osteocalcin, and AP, while concurrently reducing bone resorption markers, like the urinary DPD/creatinine ratio and plasmatic TRAP.
- SEM images revealed a notable improvement in microfractures in OVX mice treated with VK compared to untreated controls.
- SHAM Operated VK Treated displayed a higher number of migrating osteoblasts and enhanced in situ secretion of AP. OVX resulted in a decrease in in situ AP secretion, which was restored by VK treatment. Additionally, VK supplementation increased mRNA expression of bone Calbindin 28KDa independent of OVX.
Conclusion
VK treatment improved bone ultrastructure in OVX mice by enhancing osteoblastic function and organic bone matrix secretion. Therefore, VK could be a promising treatment option for patients with osteopenia/osteoporosis.
Figure 1A: DXA from average of measurements at end-point of treatment. SHAM operated VK treated mice showed increased in BMD when compared to SHAM operated Mock treated mice. As expected, OVX in SHAM operated OVX mice led to a decrease in their SHAM operated controls time course of increasing which ins reversed by VK treatment.
Figure 2A: Bone serum formation markers, Osteocalcin – matrix Gla protein measured by either ELISA or end-point colorimetric assay, respectively (all n=6). VK treatment significantly raised serum concentrations of osteocalcin in SHAM VK treated mice whereas OVX Mock treated mice exhibited lower serum level of osteocalcin when compared to their controls (n = 4, p< 0.05). On the contrary, supplementation of OVX mice with VK according to our protocol led to a reversion of this effect in OVX mice.
Figure 3A: It was observed that VK treated enhances the mRNA of Cbp28k in 80% independently of OVX. It is known the influx of Ca2+ buffered by Cbp28k in osteoblast activate exocytosis of several matrix proteins, hence we evaluated secretion of AP in situ in femurs by histochemical methods.
Study 3 - The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children
Study details
- 8-week duration
- 55 healthy children, aged between 6 and 10 years, normal (3rd to 97th percentile) height and weight
- One group receiving a placebo, the other group receiving a supplement containing 45 mg MK-7
Measurements
- Serum levels of ucOC, cOC and MK-7 were measured at baseline and after 8 weeks, together with bone markers and coagulation parameters.
- The UCR was used as an indicator of vitamin K status.
Results
- In the MK-7-supplemented group (n 28), the circulating concentration of inactive ucOC reduced and the UCR improved whereas the concentration of MK-7 increased.
- Within the placebo group, ucOC, cOC, UCR, and MK-7 did not significantly change over time.
- In both groups, bone markers and coagulation parameters remained constant over time.
Conclusion
Modest supplementation with MK-7 increases circulating concentrations of MK-7 and osteocalcin carboxylation in healthy prepubertal children.
Figure 1: Vitamin K parameters at baseline and after 8 weeks in the placebo and vitamin K groups. Differences from baseline to follow-up in each group were examined using Wilcoxon signed-ranks tests. (a) Carboxylated osteocalcin. The differences from baseline to follow-up in the placebo and vitamin K groups were NS (P¼0·657 and P¼0·067 respectively). (b) Undercarboxylated osteocalcin. The difference from baseline to follow-up in the placebo group was NS (P¼0·228). The difference from baseline to follow-up in the vitamin K group was significant (P,0·001). (c) Undercarboxylated osteocalcin:carboxylated osteocalcin ratio (UCR). The difference from baseline to follow-up in the placebo group was NS (P¼0·451). The difference from baseline to follow-up in the vitamin K group was significant (P,0·001). (d) Serum menaquinone-7 (MK-7). The difference from baseline to follow-up in the placebo group was NS (P¼0·244). The difference from baseline to follow-up in the vitamin K group was significant (P,0·001).
Study 4 - The combined effect of vitamin K and calcium on bone mineral density in humans: a meta-analysis of randomized controlled trials
Study details
- 1346 patients from 10 randomized controlled trials
- The intervention duration of all studies: From 6 months to 4 years
- The included studies: 6 trials were conducted with vitamin K1 and 7 with vitamin K2
Results
- Vitamin K combined with calcium was associated with a higher lumbar spine BMD compared to controls. The SMD was 0.20 [95% confidence interval (CI): 0.07 to 0.32] (Fig. 1 (a) & (b)).
- Vitamin K and calcium supplementation led to a significant decrease in UcOC (SMD: - 1.71, 95% CI: - 2.45 to - 0.96) (Fig. 2).
- Subgroup analysis showed that vitamin K2 and vitamin K1 had SMDs of 0.30 (95% CI: 0.10 to 0.51) and SMDs of 0.14 (95% CI: - 0.02 to 0.29), and calcium dosages of ≤ 1000 mg/d or > 1000 mg/d had SMDs of 0.19 (95% CI: 0.05 to 0.32) and 0.26 (95% CI: - 0.04 to 0.55) (Table 1)
Conclusion
The combination of vitamin K and calcium has a positive effect on lumbar BMD and decreases the level of UcOC.
Figure 1 (a) Combined effect of vitamin K and calcium on lumbar bone density. (b) Sensitivity analysis of vitamin K and calcium on lumbar bone density
Figure 2: Effect of the combination of vitamin K and calcium on UcOC
Table 1: Subgroup analysis to investigate the effect of the type of vitamin K on the effect size of vitamin K combined with calcium on 431 lumbar spines BMD
