Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women.
We searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria.
Sixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) (P = 0.006) with VK2. The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 (P = 0.03). The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65). However, after excluding one heterogeneous study, the overall effect test showed a significant reduction in fracture incidence with VK2 (RR = 0.43, P = 0.01). In addition, this meta-analysis showed that VK2 reduced serum undercarboxylated osteocalcin (uc-OC) levels and the ratio of uc-OC to cOC in both subgroups of VK2 combined intervention and alone. However, for carboxylated osteocalcin (cOC), both subgroup analysis and overall effect test showed no significant effect of VK2 on it. And the pooled analysis of adverse reactions showed no significant difference between the VK2 and control groups (RR = 1.03, 95%CI 0.87 to 1.21, P = 0.76).
The results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength.
Patients with Polycystic ovary syndrome (PCOS) are predisposed to the development of several mental comorbidities such as depression. According to several studies, PCOS can be managed by improving insulin sensitivity. The insulin-sensitizing effect of vitamin K has been reported in recent studies. Therefore, in the current trial, we assessed the effect of administrating vitamin K2 (Menaquinone-7) on depression status in women afflicted with PCOS.
Eighty-four PCOS women were allocated into the intervention and comparison groups; the intervention group (n = 42) administered 90 µg/day Menaquinone-7, and the comparison group (n = 42) consumed placebo capsules (containing avesil) for 8 weeks. In this randomized, double blind, placebo-controlled clinical trial, depression status was measured by BECK depression inventory-II (BDI-II) before and after 8 weeks of intervention.
Consumption of Menaquinone-7 in comparison with the placebo capsules significantly improved depression status (P = 0.012).
This clinical study reported the advantageous effect of Menaquinone-7 administration on depression status in PCOS patients. Trial registration The present study was registered at http://www.IRCT.ir on 06/06/2018 (registration number: IRCT20170916036204N5).
Vitamin K2 supplementation has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, but further proof for the effectiveness of this practice is still needed.
To investigate whether vitamin K2 supplementation plays a role in maintaining bone mineral density (BMD) and reducing the incidence of fractures for postmenopausal women with osteoporosis at a long-term follow-up.
We searched systematically throughout the databases of PubMed, Cochrane library, and EMBASE from the dates of their inception to November 16 2021 in this meta-analysis and systematic review, using keywords vitamin K2 and osteoporosis.
Nine RCTs with 6853 participants met the inclusion criteria. Vitamin K2 was associated with a significantly increased percentage change of lumbar BMD and forearm BMD (WMD 2.17, 95% CI [1.59-2.76] and WMD 1.57, 95% CI [1.15-1.99]). There were significant differences in undercarboxylated osteocalcin (uc-OC) reduction (WMD -0.96, 95% CI [-0.70 to 0.21]) and osteocalcin (OC) increment (WMD 26.52, 95% CI [17.06-35.98]). Adverse reaction analysis showed that there seemed to be higher adverse reaction rates in the vitamin K2 group (RR = 1.33, 95% CI [1.11-1.59]), but no serious adverse events related to vitamin K2 supplementation.
This meta-analysis and systematic review seemed to support the hypothesis that vitamin K2 plays an important role in the maintenance and improvement of BMD, and it decreases uc-OC and increases OC significantly at a long-term follow-up. Vitamin K2 supplementation is beneficial and safe in the treatment of osteoporosis for postmenopausal women.
Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease.
A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest.
A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups.
We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible.
Type 2 diabetes mellitus (T2DM) is a common disorder that is characterized by chronic hyperglycemia and chronic inflammation, which also have a reinforcing effect on each other. The present research studied the effects of menaquinone (MK-7) supplementation on serum dp-ucMGP (dephospho uncarboxylated Matrix Gla Protein), PIVKAII (Prothrombin Induced by Vitamin K Absence), inflammatory markers and body composition indices in type 2 diabetes mellitus (T2DM) patients.
This 12-week double-blind placebo-controlled randomized clinical trial allocated 60 T2DM patients equally into a MK-7 (200 mcg/day) group or a placebo group. All patients also received dietary advice at the beginning of study and their dietary intakes were checked using a 3-day food record. The body composition of each patient was also measured and their vitamin K status was assessed using the ELISA method to measure serum dp-ucMGP and PIVKAII. In addition, inflammatory status indices were also measured, including hsCRP (high-sensitivity C-reactive protein), IL-6 (interleukin-6) and TNF-α (tumor necrosis factor alpha). All measurements were made both before and after the intervention period.
In total 45 patients completed the trial (MK-7 group = 23 and placebo group = 22). The calorie and macronutrient intake of the two groups were similar pre and post intervention. There were statistically significant increases in dietary vitamin K intake for both groups over the course of the study (p < 0.05), but the intergroup differences were not significant. The body composition indices (i.e., body fat percentage, fat mass, fat free mass, muscle mass, bone mass and total body water) were not significantly different between groups or across the trial. The serum levels of the vitamin K markers, PIVKAII and dp-ucMGP, decreased significantly in the MK-7 group over the course of the study (p < 0.05), but there was no decrease in the placebo group. However, after adjusting for the baseline levels and changes in vitamin K intake, the between group differences were only significant for PIVKAII (p < 0.05). Following the intervention, the serum levels of the inflammatory markers (hsCRP, IL-6, and TNF-α) were significantly lower in the MK-7 group (p < 0.05), but not in the placebo group. However, the between group differences in the inflammatory markers were not statistically significant.
Although further studies are needed, it appears that MK-7 supplementation can be effective in improving PIVKAII levels, but not for improving dp-ucMGP, inflammatory status or the body composition indices of T2DM patients.
Muscle cramps occur in 33% to 78% of patients with dialysis. The etiology of muscle cramps is poorly understood, and no clear evidence-based prevention or treatment strategies exist. Improved interventions are urgently needed. The aim of this study was to investigate the effect of vitamin K2 in reducing the frequency and severity of muscle cramps in hemodialysis (HD) patients.
This multicenter, randomized, placebo-controlled, crossover clinical trial was conducted from June 2019 to May 2020. Each participant received vitamin K2 (360 µg/d) or placebo for two 4-wk phases, and then crossed to the alternative arm for two 4-wk phases after a 2-wk washout. The primary endpoint was the frequency of muscle cramps during HD. The secondary endpoints were severity and duration of muscle cramps during HD.
A total of 523 patients with maintenance HD were screened for muscle cramps, including 41 patients with muscle cramps refractory to conventional interventions, were enrolled. Nineteen patients in the vitamin K2-initial group and 20 in the placebo-initial group completed the protocol, and were included in the final analysis. Vitamin K2 reduced the frequency, duration, and severity of muscle cramps in HD patients (all P < 0.05). The frequency, duration, and severity of muscle cramps in HD patients increased again after crossing over to the placebo. There were no serious adverse events. One patient experienced gastrointestinal discomfort when taking vitamin K2.
This pilot trial demonstrated that vitamin K2 supplementation could decrease the frequency, duration, and severity of muscle cramps in HD patients.