The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial.

This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. PURPOSE: Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment. METHODS: We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed. RESULTS: Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03). CONCLUSION: The addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed. TRIAL REGISTRATION: The study was registered at Clinicaltrial.gov:NCT01232647.

Evaluation of Response to High-Dose Intravenous Vitamin K Administration.

BACKGROUND: Essential to the coagulation pathway, vitamin K (phytonadione) is used to correct clotting factor deficiencies and for reversal of warfarin-induced bleeding. In practice, high-dose intravenous (IV) vitamin K is often used, despite limited evidence supporting repeated dosing. OBJECTIVE: This study sought to characterize differences in responders and nonresponders to high-dose vitamin K to guide dosing strategies. METHODS: This was a case-control study of hospitalized adults who received vitamin K 10 mg IV daily for 3 days. Cases were represented by patients who responded to the first dose of IV vitamin K and controls were nonresponders. The primary outcome was change in international normalized ratio (INR) over time with subsequent vitamin K doses. Secondary outcomes included factors associated with response to vitamin K and incidence of safety events. The Cleveland Clinic Institutional Review Board approved this study. RESULTS: There were 497 patients included, and 182 were responders. Most patients had underlying cirrhosis (91.5%). In responders, the INR decreased from 1.89 at baseline (95% CI = [1.74-2.04]) to 1.40 on day 3 (95% CI = [1.30-1.50]). In nonresponders, the INR decreased from 1.97 (95% CI = [1.83-2.13]) to 1.85 ([1.72-1.99]). Factors associated with response included lower body weight, absence of cirrhosis, and lower bilirubin. There was a low incidence of safety events observed. CONCLUSIONS: In this study of mainly patients with cirrhosis, the overall adjusted decrease in INR over 3 days was 0.3, which may have minimal clinical impact. Additional studies are needed to identify populations who may benefit from repeated daily doses of high-dose IV vitamin K.

Three Different Regimens for Vitamin K Birth Prophylaxis in Infants Born Preterm: A Randomized Clinical Trial.

OBJECTIVE: To study the efficacy of 3 different vitamin K birth prophylaxis regimens in infants born premature. STUDY DESIGN: This was an open-label, parallel-group, randomized clinical trial conducted in a tertiary neonatal care unit in India. Infants born very preterm (≤32 weeks) and/or with very low birth weight (≤1500 g) were included. In each arm, 25 babies were enrolled. Babies were randomized to receive 1.0 mg, 0.5 mg, or 0.3 mg intramuscular (IM) vitamin K1 at birth. Protein induced by vitamin K absence - II (PIVKA-II) levels were assessed at birth, and on days 5 and 28, along with the frequency of death, bleeding manifestations, intraventricular hemorrhage, necrotizing enterocolitis, bilirubin levels, and duration of phototherapy. The primary outcome was comparison of PIVKA-II levels on day 5 of life. RESULTS: All the 3 regimens resulted in similar proportion of vitamin K subclinical sufficiency (PIVKA-II < 0.028 AU/mL) infants on day 5 (1 mg - 100%; 0.5 mg - 91.7%; 0.3 mg - 91.7%, P = .347), with no significant difference in median (IQR) PIVKA-II levels (AU/mL): 1 mg 0.006 (0.004, 0.009); 0.5 mg 0.008 (0.004, 0.009); 0.3 mg 0.006 (0.003, 0.009), P = .301. However, on day 28, there was a significant decrease in the proportion of vitamin K-sufficient infants in the 0.3-mg IM group (72.7%) compared with the 1.0-mg (100%) or 0.5-mg (91.3) groups. The 1.0-mg group had significantly greater bilirubin levels and duration of phototherapy. None of the other clinical outcomes were statistically different. CONCLUSIONS: Both 1-mg and 0.5-mg IM vitamin K birth prophylaxis resulted in high sufficiency on follow-up, compared with 0.3 mg. The current recommendation of 0.5-1 mg IM vitamin K birth prophylaxis for infants born preterm, needs to be continued. TRIAL REGISTRATION: CTRI/2022/02/040396.

Vitamin K Deficiency in the Setting of Blenderized Tube Feeding Regimen in a Teenager: A Case Report.

Vitamin K acts a cofactor for the gamma-carboxylation of several proteins in the coagulation cascade. The clinical spectrum of vitamin K deficiency (VKD) can be asymptomatic to a significant bleeding. VKD is classically seen in newborns. However, this can manifest later in patients with risks such as sub-optimal nutrition, fat malabsorption, medications including antibiotics. A 17-year-old male with spinal muscular atrophy (SMA) Type 1, tracheostomy with ventilator dependent, gastrostomy tube feeding was seen by the gastroenterologist following treatment for small intestinal bacterial overgrowth (SIBO). Investigations showed coagulopathy following which he was transferred to the Pediatric ICU. Labs revealed prothrombin time (PT) 114 s [Normal 9.4-12.5 s], INR (International normalized ratio) 12.6 [Normal < 1.1] and partial thromboplastin time (PTT) 90 s [Normal 25.1-36.5 s]. Mixing studies and coagulation assays were consistent with VKD (low Factor VII and Factor IX with normal Factor V). His home blenderized feeding regimen met the caloric requirement but not the adequate intake (AI) values for vitamin K and other minerals. He received intravenous vitamin K (phytonadione) for five consecutive days with resolution of the coagulopathy (PT 13.2 s, PTT 37.1 s, INR 1.2). The patient was discharged on enteral vitamin K and additional supplements following dietary review by a nutritionist. Clinicians should be cognizant of VKD in patients on blenderized tube feeds which may not meet the adequate intake (AI) goals. In patients who are not receiving nutritionally complete formulas or receiving inadequate volumes, it is important to monitor macro and micronutrients.

Role of Vitamin K in Chronic Kidney Disease: A Focus on Bone and Cardiovascular Health.

Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic disturbances, bone tissue and metabolism alterations, and vascular calcification (VC) exists and has been defined as chronic kidney disease-mineral and bone disorder (CKD-MBD). Poor vitamin K status seems to have a key role in the progression of CKD, but also in the onset and advance of both bone and cardiovascular complications. Three forms of vitamin K are currently known: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC. This review focuses on the biochemical and functional characteristics of vitamin K vitamers, suggesting this nutrient as a possible marker of kidney, CV, and bone damage in the CKD population and exploring its potential use for promoting health in this clinical setting. Treatment strategies for CKD-associated osteoporosis and CV disease should include vitamin K supplementation. However, further randomized clinical studies are needed to assess the safety and the adequate dosage to prevent these CKD complications.

Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure.

BACKGROUND: Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC. METHODS: We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (µCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies. RESULTS: The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by µCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2-treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2-treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress. CONCLUSION: In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Altered vitamin K biodistribution and metabolism in experimental and human chronic kidney disease.

Chronic kidney disease (CKD) is accompanied with extensive cardiovascular calcification, in part correlating with functional vitamin K deficiency. Here, we sought to determine causes for vitamin K deficiency beyond reduced dietary intake. Initially, vitamin K uptake and distribution into circulating lipoproteins after a single administration of vitamin K1 plus K2 (menaquinone 4 and menaquinone 7, respectively) was determined in patients on dialysis therapy and healthy individuals. The patients incorporated very little menaquinone 7 but more menaquinone 4 into high density lipoprotein (HDL) and low-density lipoprotein particles than did healthy individuals. In contrast to healthy persons, HDL particles from the patients could not be spiked with menaquinone 7 in vitro and HDL uptake was diminished in osteoblasts. A reduced carboxylation activity (low vitamin K activity) of uremic HDL particles spiked with menaquinone 7 vs. that of controls was confirmed in a bioassay using human primary vascular smooth muscle cells. Kidney menaquinone 4 tissue levels were reduced in 5/6-nephrectomized versus sham-operated C57BL/6 mice after four weeks of a vitamin K rich diet. From the analyzed enzymes involved in vitamin K metabolism, kidney HMG-CoA reductase protein was reduced in both rats and patients with CKD. In a trial on the efficacy and safety of atorvastatin in 1051 patients with type 2 diabetes receiving dialysis therapy, no pronounced vitamin K deficiency was noted. However, the highest levels of PIVKA-II (biomarker of subclinical vitamin K deficiency) were noted when a statin was combined with a proton pump inhibitor. Thus, profound disturbances in lipoprotein mediated vitamin K transport and metabolism in uremia suggest that menaquinone 7 supplementation to patients on dialysis therapy has reduced efficacy.

Development of the BioHybrid Assay: Combining Primary Human Vascular Smooth Muscle Cells and Blood to Measure Vascular Calcification Propensity.

BACKGROUND: Vascular calcification is an active process that increases cardiovascular disease (CVD) risk. There is still no consensus on an appropriate biomarker for vascular calcification. We reasoned that the biomarker for vascular calcification is the collection of all blood components that can be sensed and integrated into a calcification response by human vascular smooth muscle cells (hVSMCs). METHODS: We developed a new cell-based high-content assay, the BioHybrid assay, to measure in vitro calcification. The BioHybrid assay was compared with the o-Cresolphthalein assay and the T50 assay. Serum and plasma were derived from different cohort studies including chronic kidney disease (CKD) stages III, IV, V and VD (on dialysis), pseudoxanthoma elasticum (PXE) and other cardiovascular diseases including serum from participants with mild and extensive coronary artery calcification (CAC). hVSMCs were exposed to serum and plasma samples, and in vitro calcification was measured using AlexaFluor®-546 tagged fetuin-A as calcification sensor. RESULTS: The BioHybrid assay measured the kinetics of calcification in contrast to the endpoint o-Cresolphthalein assay. The BioHybrid assay was more sensitive to pick up differences in calcification propensity than the T50 assay as determined by measuring control as well as pre- and post-dialysis serum samples of CKD patients. The BioHybrid response increased with CKD severity. Further, the BioHybrid assay discriminated between calcification propensity of individuals with a high CAC index and individuals with a low CAC index. Patients with PXE had an increased calcification response in the BioHybrid assay as compared to both spouse and control plasma samples. Finally, vitamin K1 supplementation showed lower in vitro calcification, reflecting changes in delta Agatston scores. Lower progression within the BioHybrid and on Agatston scores was accompanied by lower dephosphorylated-uncarboxylated matrix Gla protein levels. CONCLUSION: The BioHybrid assay is a novel approach to determine the vascular calcification propensity of an individual and thus may add to personalised risk assessment for CVD.

Nutritional Therapy with Vitamin K1 Is Effective in the Improvement of Vitamin K Status and Bone Turnover Markers in Patients with Severe Motor and Intellectual Disabilities.

We have previously reported that patients with severe motor and intellectual disabilities (SMID) have a high prevalence of vitamin K deficiency both in the liver and bone. Thus, vitamin K therapy for SMID patients should be considered. In the present study, we have studied the efficacy of nutritional therapy with vitamin K1 for improving their vitamin K status and bone metabolism markers in patients with SMID. During the 3-mo period, 19 patients under enteral feeding received vitamin K1 treatment, the dose of which was determined to meet each subject's energy requirement. Biomarkers of vitamin K insufficiency; protein induced by vitamin K absence or antagonist-II (PIVKA-II), undercarboxylated osteocalcin (ucOC), intact osteocalcin (intact OC) and bone turnover markers (tartrate-resistant acid phosphatase-5b: TRACP-5b and bone alkaline phosphatase: BAP) were measured at baseline and post treatment. The ucOC/OC ratio was calculated as a more sensitive index than ucOC for vitamin K status in the bone. After treatment, the median vitamin K intake increased from 66 to 183 µg/d, and serum levels of PIVKA-II and ucOC/OC ratio were significantly decreased. Decrements of serum ucOC level and ucOC/OC ratio were significantly associated with vitamin K intake, indicating that both markers well reflect the dose-dependent vitamin K effects. Serum levels of BAP and TRACP-5b were significantly increased after vitamin K1 therapy. Nutritional therapy with vitamin K1 effectively improved the markers for vitamin K status and bone turnover, and was considered to be a good candidate for treatment in SMID patients.

Evaluation of vitamin K status and rationale for vitamin K supplementation in dialysis patients.

The cardinal biological role of vitamin K is to act as cofactor for the carboxylation of a number of vitamin K-dependent proteins, some of which are essential for coagulation, bone formation and prevention of vascular calcification. Functional vitamin K deficiency is common and severe among dialysis patients and has garnered attention as a modifiable risk factor in this population. However, no single biochemical parameter can adequately assess vitamin K status. For each biological function of vitamin K, the degree of carboxylation of the relevant vitamin K-dependent protein most accurately reflects vitamin K status. Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) is the best biomarker for vascular vitamin K status when cardiovascular endpoints are studied. Dp-ucMGP levels are severely elevated in haemodialysis patients and correlate with markers of vascular calcification and mortality in some but not all studies. The aetiology of vitamin K deficiency in haemodialysis is multifactorial, including deficient intake, uraemic inhibition of the vitamin K cycle and possibly interference of vitamin K absorption by phosphate binders. The optimal vitamin K species, dose and duration of supplementation to correct vitamin K status in dialysis patients are unknown. Dp-ucMGP levels dose-proportionally decrease with supraphysiological vitamin K2 supplementation, but do not normalize even with the highest doses. In the general population, long-term vitamin K1 or K2 supplementation has beneficial effects on cardiovascular disease, bone density and fracture risk, and insulin resistance, although some studies reported negative results. In haemodialysis patients, several trials on the effects of vitamin K on surrogate markers of vascular calcification are currently ongoing.

Adherence to Long-Term Follow-Up of Patients with Life-Threatening, Inhaled Synthetic Cannabinoids-Associated Coagulopathy in Chicago.

A large-scale outbreak of life-threatening, inhaled synthetic cannabinoids (Spice/K2)-associated coagulopathy with bleeding complications was recently reported in Illinois. The causative agents were brodifacoum, difenacoum, and bromadiolone, potent, long-acting, 4-hydroxycoumarin anticoagulant rodenticides (LAAR) that were mixed with Spice/K2 products procured and then inhaled by the victims. We report on 3 poisoned patients who reside in underserved, socioeconomically disadvantaged neighborhoods of Chicago that were admitted and treated successfully at two inner-city, tertiary care hospitals in Chicago. The patients were discharged from the hospitals on daily long-term high-dose oral vitamin K1 (VK1), provided free of charge. However, 2 patients were lost to follow-up prior to safe discontinuation of oral VK1 therapy. The third patient was treated and followed successfully for 7 months when VK1 was discontinued. We conclude that prolonged oral VK1 therapy and follow-up of acute, life-threatening LAAR poisoning are variable and present challenges to healthcare providers. Appropriate practice guidelines to improve patient access and adherence to daily high-dose oral VK1 therapy and follow-up should be developed and implemented.

Effects of nutritional intervention upon bone turnover in elderly hip fracture patients. Randomized controlled trial.

BACKGROUND AND AIM: Hip fracture patients are at great risk of malnutrition, but documentation of the effect of nutrition supplementation in this group is sparse and inconclusive. The aim of this study was to examine if personalized nutrition advice combined with vitamin K1, Ca and vitamin D could improve bone turnover 4 months after hip fracture. DESIGN: This is a preplanned sub study of a randomized controlled trial of orthogeriatric care. The intervention group received orthogeriatric care, including nutrition advice and supplementation. The control group received usual care at the orthopedic ward. Blood was drawn for measurements of a number of vitamins and of bone turnover markers upon admission and at four months follow up. RESULTS: 71 patients (31 in the intervention group and 40 controls) had available data at 4 months as well as at baseline. After four months, vitamin K1 and 25(OH)D were higher in the intervention group compared with controls; vitamin K1: 1.0 ± 1.2 vs 0.6 ± 0.6 ng/ml, p = 0.09, 25(OH)D: 60 ± 29 vs 43 ± 22 nmol/L, p = 0.01 when adjusted for baseline differences. In a secondary, unadjusted analysis, comprising all patients with available four months data (n = 136), the differences were statistically significant for vitamin K1 as well as 25(OH)D (p = 0.03 and p < 0.001, respectively). There was a non-significant increase in 25(OH)D in the intervention group from baseline to 4 months follow up, and a significant decrease in the control group. There was no difference in bone turnover markers between the two groups at 4 months follow up. A substantial loss of weight and physical function was found in both groups. CONCLUSIONS: The supplementation of 25(OH)D and vitamin K1 improved serum concentrations of these vitamins, but this did not translate into any improvement in the bone turnover markers. The RCT is registered in ClinicalTrials.govNCT01009268 and NCT01738776.

α-Tocopherol Intake Decreases Phylloquinone Concentration in Bone but Does Not Affect Bone Metabolism in Rats.

Previous studies have shown that α-tocopherol intake lowers phylloquinone (PK) concentration in some extrahepatic tissues in rats. The study's aim was to clarify the effect of α-tocopherol intake on vitamin K concentration in bone, as well as the physiological action of vitamin K. Male Wistar rats were divided into 4 groups. Over a 3-mo period, the K-free group was fed a vitamin K-free diet with 50 mg RRR-α-tocopherol/kg, the E-free group was fed a diet containing 0.75 mg PK/kg without vitamin E, the control group was fed a diet containing 0.75 mg PK/kg with 50 mg RRR-α-tocopherol/kg, and the E-excess group was fed a diet containing 0.75 mg PK/kg with 500 mg RRR-α-tocopherol/kg. PK concentration in the liver was higher in E-excess rats than in E-free rats, was lower in the tibias of control rats than in those of E-free rats, and was lower in E-excess rats than in control rats. Menaquinone-4 (MK-4) concentration in the liver was higher in E-excess rats than in E-free and control rats. However, MK-4 concentrations in the tibias of E-free, control, and E-excess rats were almost the same. Blood coagulation activity was lower in K-free rats than in the other rats but was not affected by the level of α-tocopherol intake. Additionally, dietary intake of PK and α-tocopherol did not affect uncarboxylated-osteocalcin concentration in the serum, femur density, or expression of the genes related to bone resorption and formation in the femur. These results suggest that α-tocopherol intake decreases PK concentration in bone but does not affect bone metabolism in rats.

Effect of 1-y oral supplementation with vitaminized olive oil on platelets from healthy postmenopausal women.

OBJECTIVE: Olive oil is the main fat source in the Mediterranean diet and shows a protective role against aging and related diseases. Osteoporosis represents a serious health problem worldwide and is associated with an increased risk for fractures and mortality. Nutrition should be part of bone disease prevention strategies, especially in light of the aging population and the effect of diet on bone health. The aim of this study was to investigate whether oral supplementation with extra virgin olive oil (VOO) enriched with vitamins D3, K1, and B6 (VitVOO) is able to modify some physicochemical and functional plasma membrane properties and nitrosative stress markers status. METHODS: In this single-center, randomized placebo-controlled trial, 60 postmenopausal women were administered either VitVOO or placebo (PlaVOO). After 1 y of oral supplementation, platelet membrane fluidity changes, Na+/K+-ATPase activity, serum nitric oxide, and peroxynitrite levels were determined in participants. RESULTS: After 1 y (time 1), women taking VitVOO showed lower nitric oxide levels than those taking PlaVOO; the same trend was found for peroxynitrite levels. As far as membrane fluidity was concerned, a significant decrease in anisotropy of diphenylhexatriene and trimethylammonium-diphenylhexatriene at time 1 in VitVOO participants compared with PlaVOO was found. Finally, Na+/K+-ATPase activity showed a significant increase after VitVOO supplementation. CONCLUSION: The supplementation of VitVOO into the diet of postmenopausal women could represent a proper tool for platelet function and a useful strategy against nitrosative stress and related diseases, thus confirming the antioxidant role played by the added vitamins.

Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA. MATERIALS AND METHODS: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention. RESULTS: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05). CONCLUSIONS: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.

[EMERGENCY TREATMENT OF BLEEDING IN PATIENTS TAKING WARFARIN].

Anticoagulant therapy with vitamin K antagonists (AVK) is an effective treatment and prevention of thrombosis. One of the major disadvantages of the AVK is a risk for serious bleeding. Prothrombin complex concentrates (PCC), fresh frozen plasma (FFP) and vitamin K1 are available for control of these situations. The experience of special team ofthe Scientific Center for Hematology was the basis for presented retrospective study. Three regimens of warfarin-related bleeding were compared: PCC+ VK for several bleeding, FFP+ VK for different clinical situations and VKfor light bleeding. PCC showed himself as effective and safe hemostatic agent. Transfusions of FFP were sometimes not effective, sometimes led to TACO. Supplementation of vitamin K1 for patients of I and II groups provided more stable control of hemostasis. In III group VK vas effective to stop bleeding. Two impotent sings for conclusion: necessary of laboratory monitoring, TEG first of all; individual balance of hemostasis base of bleeding or thrombotic risks.

Increase in plasma phylloquinone concentrations following acupoint injection for the treatment of primary dysmenorrhea.

The therapeutic benefits of acupoint injection of vitamin K in spleen-6 (SP6) for the treatment of primary dysmenorrhea have been observed in limited clinical settings. However, menadione, the form of vitamin K most studied for treating dysmenorrhea, is not routinely used in clinical practice in North America. As part of a larger clinical trial among women aged 18-25 years with primary dysmenorrhea, we conducted a substudy to test the plasma concentration of phylloquinone (vitamin K1). We collected blood samples from four women before and 24-48 hours after an acupoint injection of phylloquinone in SP6. Despite the rapid turnover of phylloquinone observed in previous studies, we found that the plasma phylloquinone concentrations increased significantly from preinjection to 1-2 days after the injection. Interestingly, higher phylloquinone concentrations were correlated with less pain intensity among women with dysmenorrhea. Additional research is needed to understand the association between vitamin K and menstrual pain, including the role of vitamin K deficiency in inflammation and pain, and on the possible mechanisms of acupoint injection of vitamin K for the treatment of primary dysmenorrhea.

Excess α-tocopherol decreases extrahepatic phylloquinone in phylloquinone-fed rats but not menaquinone-4 in menaquinone-4-fed rats.

SCOPE: The effects of vitamin E on vitamin K metabolism were elucidated by comparing the effect of tocopherol intake on vitamin K concentrations in rats fed phylloquinone (PK) or menaquinone (MK)-4. METHODS AND RESULTS: Initially, the dietary effect of RRR-α-tocopherol, but not RRR-γ-tocopherol, in decreasing extrahepatic PK concentrations was confirmed. Subsequently, rats were fed a PK or MK-4-containing diet (0.75 mg/kg) with RRR-α-tocopherol (0, 10, 50, or 500 mg/kg) for 6 weeks. In rats fed PK, α-tocopherol consumption decreased PK in kidney, lung, heart, muscle, testis, and brain but not in serum and liver. However, in rats fed MK-4, α-tocopherol consumption did not decrease MK-4 in serum and tissues. Finally, vitamin K- and E-depleted rats were administered PK or MK-4 (0.2 mg) with RRR-α-tocopherol (0, 1, or 10 mg) by gavage. After PK administration, α-tocopherol was observed to decrease PK in kidney, adrenal gland, lung, testis, and brain but not in serum and liver, whereas, after MK-4 administration, α-tocopherol did not affect MK-4 in serum and tissues. CONCLUSION: Excess α-tocopherol decreased extrahepatic PK in rats fed PK but not MK-4 in rats fed MK-4.

Prolonged coagulopathy after brodifacoum exposure.

PURPOSE: A case of brodifacoum exposure leading to coagulopathy lasting for approximately one year despite treatment with large doses of phytonadione is reported. SUMMARY: A 36-year-old man was diagnosed with severe coagulopathy. He was treated and discharged on 40 mg of oral phytonadione daily. The cause of the coagulopathy remained unknown at discharge, but the hematologist theorized that exposure to a vitamin K antagonist was likely the source of the patient's condition. The patient was rehospitalized one week later with an International Normalized Ratio (INR) of 5.9 despite self-reported medication compliance. Oral phytonadione was increased to 80 mg daily. The patient was seen at an outpatient hematology clinic for several months and continued on tapering dosages of oral phytonadione. A coagulopathy panel from the original hospitalization confirmed the presence of brodifacoum, though the method of exposure remained unclear. He was lost to follow-up until approximately nine months later, when he reported taking 10 mg daily of oral phytonadione and had an INR of 1. Oral phytonadione was discontinued. Two months later, his INR was greater than 9, despite an undetectable level of brodifacoum. He was rehospitalized with oropharyngeal hematoma approximately 1 year after the initial coagulopathy diagnosis. The patient was discharged on 40 mg oral phytonadione daily with outpatient follow-up. CONCLUSION: A patient with brodifacoum exposure ingested brodifacoum had coagulopathy that lasted approximately one year despite long-term treatment with large dosages of oral phytonadione. The coagulopathy persisted even when brodifacoum was undetectable in the serum. Long-term treatment with high-dose phytonadione is expensive, which may influence medication compliance.

An innovative acupuncture treatment for primary dysmenorrhea: a randomized, crossover pilot study.

CONTEXT: Dysmenorrhea, the occurrence of painful menstrual cramping of the uterus, is a major cause of activity restriction and absences from school and work among young women. Standard pharmaceuticals used to treat dysmenorrhea are not effective for all women and have side effects that limit their use. Studies elsewhere have shown beneficial effects for use of vitamin K1 as an acupoint treatment, but the acceptability of this treatment to women in the United States has been unknown. OBJECTIVE: The study intended to examine the feasibility, acceptability, and preliminary effects of acupuncture point injection of vitamin K1 as an alternative treatment for primary dysmenorrhea among US women. DESIGN: The research team conducted a pilot study using a blinded, randomized, crossover trial design. SETTING: The study took place at the University of California, San Francisco (UCSF). PARTICIPANTS: The study was conducted in the San Francisco Bay Area among women 18 to 25 y of age who had been diagnosed with primary dysmenorrhea. Fourteen women completed all of the study's visits. INTERVENTION: Women with primary dysmenorrhea were randomized into 2 groups to receive bilateral injections of vitamin K1 in the Spleen-6 (SP-6) acupuncture point at the start of menstruation and then, following a 2-mo washout period, saline in a nonacupuncture point at the start of menstruation. One group received the vitamin K1 injection first, while the other group received the saline injection first. OUTCOME MEASURE: Dysmenorrhea pain intensity was measured using a 0-10 numeric rating scale (NRS), before and after injections. RESULTS: Women had an average 2.5-point decrease in pain after a vitamin K1 injection in the SP-6 acupoint (P < .001), as compared with a 1.8-point decrease after a saline injection (P < .001). Change scores for vitamin K1, as compared with a saline injection, approached statistical significance (P < .10). Intensity and duration of menstrual symptoms, as measured by the Cox retrospective symptom scale, also decreased following injections. After participating, 94% of the women remained agreeable to receiving the injection therapy, and 77% reported they would come every month were the treatment available. CONCLUSIONS: Findings suggested high acceptability for an acupuncture point injection of vitamin K1 as treatment for primary dysmenorrhea among young women in San Francisco. Pain decreased with both treatments, with a trend toward greater pain reduction for the vitamin K1/SP-6 injection. This finding is consistent with outcomes from the Obstetrics and Gynecology Hospital in Shanghai, China, where the protocol was developed.