Post-bariatric pregnancy is associated with vitamin K1 deficiency, a case control study.

BACKGROUND: Maternal obesity is associated with adverse outcome for pregnancy and childbirths. While bariatric surgery may improve fertility and reduce the risk of certain pregnancy-related complications such as hypertension and gestational diabetes mellitus, there is a lack of evidence on the optimal nutritional monitoring and supplementation strategies in pregnancy following bariatric surgery. We aimed to assess the impact of bariatric surgery on micronutrients in post-bariatric pregnancy and possible differences between gastric bypass surgery and sleeve gastrectomy. METHODS: In this prospective case control study, we recruited 204 pregnant women (bariatric surgery n = 59 [gastric bypass surgery n = 26, sleeve gastrectomy n = 31, missing n = 2] and controls n = 145) from Akershus university hospital in Norway. Women with previous bariatric surgery were consecutively invited to study participation at referral to the clinic for morbid obesity and the controls were recruited from the routine ultrasound screening in gestational week 17-20. A clinical questionnaire was completed and blood samples were drawn at mean gestational week 20.4 (SD 4.5). RESULTS: The women with bariatric surgery had a higher pre-pregnant BMI than controls (30.8 [SD 6.0] vs. 25.2 [5.4] kg/m2, p < 0.001). There were no differences between groups regarding maternal weight gain (bariatric surgery 13.3 kg (9.6) vs. control 14.8 kg (6.5), p = 0.228) or development of gestational diabetes (n = 3 [5%] vs. n = 7 [5%], p = 1.000). Mean levels of vitamin K1 was lower after bariatric surgery compared with controls (0.29 [0.35] vs. 0.61 [0.65] ng/mL, p < 0.001). Multiadjusted regression analyses revealed an inverse relationship between bariatric surgery and vitamin K1 (B -0.26 ng/mL [95% CI -0.51, -0.04], p = 0.047) with a fivefold increased risk of vitamin K1 deficiency in post-bariatric pregnancies compared with controls (OR 5.69 [1.05, 30.77] p = 0.044). Compared with sleeve gastrectomy, having a previous gastric bypass surgery was associated with higher risk of vitamin K1 deficiency (OR 17.1 [1.31, 223.3], p = 0.030). CONCLUSION: Post-bariatric pregnancy is negatively associated with vitamin K1 with a higher risk of vitamin K1 deficiency in pregnancies after gastric bypass surgery compared with after sleeve gastrectomy. Vitamin K1 deficiency in post-bariatric pregnancy have potential risk of hypocoaguble state in mother and child and should be explored in future studies.

Stability and bioaccessibility of micronutrients and phytochemicals present in processed leek and Brussels sprouts during static in vitro digestion.

Vegetables are frequently processed before consumption. However, vegetable functionalization continues beyond ingestion as the human digestive tract exposes vegetable products to various conditions (e.g. elevated temperature, pH alterations, enzymes, electrolytes, mechanical disintegration) which can affect the stability of micronutrients and phytochemicals. Besides the extent to which these compounds withstand the challenges posed by digestive conditions, it is equally important to consider their accessibility for potential absorption by the body. Therefore, this study investigated the impact of static in vitro digestion on the stability (i.e. concentration) and bioaccessibility of vitamin C, vitamin K1, glucosinolates, S-alk(en)yl-l-cysteine sulfoxides (ACSOs) and carotenoids in Brussels sprouts (Brassica oleracea var. gemmifera) and leek (Allium ampeloprasum var. porrum). Water-soluble compounds, glucosinolates and ACSOs, remained stable during digestion while vitamin C decreased by >48%. However, all water-soluble compounds were completely bioaccessible. Lipid-soluble compounds were also stable during digestion but were only bioaccessible for 26-81%.

Impact of refrigerated storage on (bio)chemical conversions of health-related compounds in pretreated, pasteurized Brussels sprouts and leek.

Vegetable processing often consists of multiple processing steps. Research mostly focused on the impact of individual processing steps on individual health-related compounds. However, there is a need for more holistic approaches to understand the overall impact of the processing chain on the health potential of vegetables. Therefore, this work studied the impact of pretreatment (relatively intact versus pureed vegetable systems), pasteurization and subsequent refrigerated storage (kinetic evaluation) on multiple health-related compounds (vitamin C, vitamin K1, carotenoids, glucosinolates and S-alk(en)yl-L-cysteine sulfoxides (ACSOs)) in Brussels sprouts and leek. It could be shown that differences introduced by different types of pretreatment were not nullified during pasteurization and refrigerated storage. Clearly, enzymatic conversions controlled during pretreatment resulted in different health-related compound profiles still observable after pasteurization. Moreover, about -42% and -100% relative concentration differences of ACSOs and dehydroascorbic acid, respectively, were detected immediately after pasteurization, while glucosinolates concentrations decreased by about 47% during refrigerated storage. All other compounds were stable during pasteurization and refrigerated storage.

The biological responses of vitamin K2: A comprehensive review.

Vitamin K1 (VitK1) and Vitamin K2 (VitK2), two important naturally occurring micronutrients in the VitK family, found, respectively, in green leafy plants and algae (VitK1) and animal and fermented foods (VitK2). The present review explores the multiple biological functions of VitK2 from recently published in vitro and in vivo studies, including promotion of osteogenesis, prevention of calcification, relief of menopausal symptoms, enhancement of mitochondrial energy release, hepato- and neuro-protective effects, and possible use in treatment of coronavirus disease. The mechanisms of action associated with these biological effects are also explored. Overall, the findings presented here suggest that VitK, especially VitK2, is an important nutrient family for the normal functioning of human health. It acts on almost all major body systems and directly or indirectly participates in and regulates hundreds of physiological or pathological processes. However, as biological and clinical data are still inconsistent and conflicting, more in-depth investigations are warranted to elucidate its potential as a therapeutic strategy to prevent and treat a range of disease conditions.

Dynamic changes and influencing factors of vitamin K levels in neonates / 中国新生儿科杂志

Objective:To study the incidences of vitamin K 1 and K 2 deficiency (VKD) in umbilical cord blood (UBC) of neonates and the dynamic changes and influencing factors of serum vitamin K 1 levels after preventive vitamin K 1 supplementation. Methods:From January 2021 to June 2022, neonates born in the Obstetrics Department of our hospital were prospectively enrolled and the levels of vitamin K 1 and K 2 in UBC and serum vitamin K 1 levels at 14 d and 28 d after vitamin K 1 supplementation were measured. The neonates were assigned into hospitalization group and healthy group and further assigned into early-preterm, late-preterm and full-term groups based on gestational age (GA). The incidences of VKD of different GA were studied. Dynamic changes of vitamin K 1 levels were calculated. Multivariate logistic regression was used to analyze the influencing factors of vitamin K 1 levels in hospitalization group at 28 d. Results:A total of 100 neonates were included. 80 neonates were hospitalized, including 25 early-preterm, 25 late-preterm and 30 full-term. 20 were healthy full-term neonates. No significant differences existed in the incidences of VKD of different GA ( P>0.05), however, the overall incidences were high (82.0% and 84.0%, respectively). After preventive vitamin K 1 supplementation, the levels of vitamin K 1 in full-term and preterm groups at 14 d were higher than at birth and 28 d. The levels of vitamin K 1 in hospitalized full-term neonates at 14 d and 28 d were higher than hospitalized preterm neonates. The levels of vitamin K 1 at 28 d in healthy group was significantly higher than hospitalization group ( P<0.05). Multivariate logistic regression analysis showed that maternal complications during pregnancy ( OR=5.889, 95% CI 1.621-21.399, P=0.007) and neonatal antibiotic use ( OR=5.615, 95% CI 1.833-17.221, P=0.003) were risk factors and formula feeding ( OR=0.389, 95% CI 0.193-0.786, P=0.008) was a protective factor for VKD. Conclusions:VKD is common in neonates. The serum vitamin K 1 level increases significantly after preventive vitamin K 1 supplementation. The vitamin K 1 levels of hospitalized full-term neonates at 14 d and 28 d are higher than hospitalized preterm neonates. The levels of vitamin K 1 at 28 d in hospitalized neonates are influenced by feeding methods, maternal complications during pregnancy and neonatal antibiotic use.

Cutaneous allergic reaction to subcutaneous vitamin K1: A case report and review of literature.

BACKGROUND: Vitamin K1 (phytomenadione) is a fat-soluble naturally occurring vitamin that is widely used to treat certain coagulation disorders. Adverse cutaneous reactions to vitamin K1 can occur; however, owing to its low incidence and considerable variability in presentation and morphology, its diagnosis can be easily overlooked. Managing these reactions may be challenging for patients and clinicians. Therefore, reviewing the adverse cutaneous reactions to vitamin K1 is important. CASE SUMMARY: Here we report the case of a 50-year-old woman with no pre-existing hepatic disease who developed a cutaneous allergic reaction to subcutaneous vitamin K1 that presented as localized eczematous plaques at the vitamin K1 injection site. The eruption developed within 5 d of the injection and persisted for 32 mo despite treatment with topical and intralesional steroids. Eczema was diagnosed based on the results of the pathological examination, immunohistochemical staining, and a skin biopsy. The patient was advised to take herbal medicines orally twice daily. After treatment and follow-up, the patient's eczematous urticarial plaques improved and her condition stabilized. CONCLUSION: Here we present the first case of a cutaneous allergic reaction to subcutaneous vitamin K1 that was successfully treated with Chinese medicine.

Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth.

BACKGROUND: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1 ) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth. OBJECTIVES: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla proteins, factor II (PIVKA-II), and osteocalcin (GluOC), synthesized by liver and bone, respectively. PATIENTS/METHODS: Prospective, multicenter, observational study in preterm infants born <33 weeks' gestation. Blood samples and dietary history were collected before hospital discharge, and after discharge at 2-3 months' corrected age. Outcome measures were serum VK1 , PIVKA-II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk-fed and formula/mixed-fed infants after discharge. RESULTS: After discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 µg/L), higher PIVKA-II (0.10 vs. 0.02 AU/ml) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only one (2%) of 45 breastmilk-fed infants was VK insufficient. After discharge, eight (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only one (4%) of 25 formula/mixed-fed babies. CONCLUSIONS: Preterm infants who remain exclusively or predominantly human breastmilk-fed after neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine postdischarge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency.

Development of a liquid chromatography mass spectrometry method for the determination of vitamin K1, menaquinone-4, menaquinone-7 and vitamin K1-2,3 epoxide in serum of individuals without vitamin K supplements.

OBJECTIVES: Vitamin K and metabolites have a beneficial role in blood coagulation, bone metabolism and growth. However, the determination of vitamin K concentrations in the blood in patients consuming a diet with naturally occurring vitamin K is currently challenging. We aim to develop a cost-effective and rapid method to measure vitamin K metabolites with potential application for clinics and research. METHODS: We developed a simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of vitamin K1, menaquinone-4 (MK-4), menaquinone-7 (MK-7) and vitamin K1-2,3 epoxide in human serum and validated the method in a study cohort of 162 patients tested for carbohydrate malabsorption and in 20 patients with oral phenprocoumon intake. RESULTS: The overall precision (CVs) ranged between 4.8 and 17.7% in the specified working range (0.06-9.0 nmol/L for all analytes except for MK-7 with 0.04-6.16 nmol/L). In the malabsorption cohort samples, measured values were obtained for all different vitamin K metabolites except for vitamin K1-2,3 epoxide. This metabolite could be detected only in patients with phenprocoumon intake. The good performance of the method is especially achieved by the interaction of three factors: the use of lipase in the sample preparation, the use of an atypical fluorinated reversed phase column, and a logarithmic methanol gradient. CONCLUSIONS: The described method is able to determine the concentration of four vitamin K metabolites in a time-efficient, simple and cost-effective manner. It can be suitable for both routine clinics and research.

Vitamin K Insufficiency in the Indian Population: Pilot Observational Epidemiology Study.

BACKGROUND: The fat-soluble K vitamins K1 and K2 play an essential role in the blood coagulation cascade and are made available predominantly through selective dietary intakes. They are less known for their nonessential roles in a family of vitamin K-dependent proteins that promote various functions of organs and systems in the body. A lack of vitamin K can characterize vitamin and nutritional element insufficiency, which is different from a clinically apparent vitamin deficiency. OBJECTIVE: This epidemiological study evaluated the nutritional status of vitamin K in a sample of the Indian population and vitamin K content in staple Indian foods. METHODS: Serum levels of vitamin K1 and vitamin K2 in the form of menaquinone-7 (MK-7) were assessed via high-performance liquid chromatography coupled with fluorescence detection in 209 patients with type 2 diabetes, 50 healthy volunteers, and common staple foods in India. RESULTS: After comparing populations with high and low serum vitamin K levels from various geographical regions, our results indicated that the sample of healthy Indian individuals and the sample of Indian patients with type 2 diabetes had low (insufficient) levels of vitamin K2 (MK-7; range 0.3-0.4 ng/mL). No significant differences existed in vitamin K1-related and MK-7-related values between healthy male and female subjects, between male and female subjects with diabetes, and between the healthy sample and the sample of patients with diabetes. The staple, commonly consumed Indian foods that were tested in this study had undetectable levels of vitamin K2, while levels of vitamin K1 varied widely (range 0-37 µg/100 g). CONCLUSIONS: Based on our sample's low serum levels of vitamin K2 (MK-7) as well as the low levels of vitamin K2 in their typical diet, we propose that the general Indian population could benefit from the consumption of vitamin K2 in the form of MK-7 supplements. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2019/05/014246; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=21660&EncHid=&userName=014246; Clinical Trials Registry - India CTRI/2019/03/018278; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=32349&EncHid=&userName=018278.

The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study.

Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and immunomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 levels have a causal effect on COVID-19 related outcomes, including risk of infection, hospitalization and critical illness. Methods: We employed a two-sample Mendelian Randomization (MR) analysis. Our genetic variants derived from European-ancestry GWAS reflected circulating levels of Zn, Cu, Se in red blood cells as well as Se and vitamin K1 in serum/plasma. For the COVID-19 outcome GWAS, we used infection, hospitalization or critical illness. Our inverse-variance weighted (IVW) MR analysis was complemented by sensitivity analyses including a more liberal selection of variants at a genome-wide sub-significant threshold, MR-Egger and weighted median/mode tests. Results: Circulating micronutrient levels show limited evidence of association with COVID-19 infection, with the odds ratio [OR] ranging from 0.97 (95% CI: 0.87-1.08, p-value = 0.55) for zinc to 1.07 (95% CI: 1.00-1.14, p-value = 0.06)-i.e., no beneficial effect for copper was observed per 1 SD increase in exposure. Similarly minimal evidence was obtained for the hospitalization and critical illness outcomes with OR from 0.98 (95% CI: 0.87-1.09, p-value = 0.66) for vitamin K1 to 1.07 (95% CI: 0.88-1.29, p-value = 0.49) for copper, and from 0.93 (95% CI: 0.72-1.19, p-value = 0.55) for vitamin K1 to 1.21 (95% CI: 0.79-1.86, p-value = 0.39) for zinc, respectively. Conclusions: This study does not provide evidence that supplementation with zinc, selenium, copper or vitamin K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.

New Insight into Vitamins E and K1 as Anti-Quorum-Sensing Agents against Pseudomonas aeruginosa.

Today, antivirulence compounds that attenuate bacterial pathogenicity and have no interference with bacterial viability or growth are introduced as the next generation of antibacterial agents. However, the development of such compounds that can be used by humans is restricted by various factors, including the need for extensive economic investments, the inability of many molecules to penetrate the membrane of Gram-negative bacteria, and unfavorable pharmacological properties and cytotoxicity. Here, we take a new and different look into two frequent supplements, vitamin E and K1, as anti-quorum-sensing agents against Pseudomonas aeruginosa, a pathogen that is hazardous to human life and responsible for several diseases. Both vitamins showed significant anti-biofilm activity (62% and 40.3% reduction by vitamin E and K1, respectively), and the expression of virulence factors, including pyocyanin, pyoverdine, and protease, was significantly inhibited, especially in the presence of vitamin E. Cotreatment of constructed biofilms with these vitamins plus tobramycin significantly reduced the number of bacterial cells sheltered inside the impermeable matrix (71.6% and 69% by a combination of tobramycin and vitamin E or K1, respectively). The in silico studies, besides the similarities of chemical structures, reinforce the possibility that both vitamins act through inhibition of the PqsR protein. This is the first report of the antivirulence and antipathogenic activity of vitamin E and K1 against P. aeruginosa and confirms their potential for further research against other multidrug-resistant bacteria.

Brodifacoum pharmacokinetics in acute human poisoning: implications for estimating duration of vitamin K therapy.

Standard of care follow-up therapy for patients poisoned by long-acting anticoagulant rodenticides (LAARs) is daily high-dose (up to 100 mg per day) oral vitamin K1 (VK1) for weeks to months to over a year. The availability of CLIA-certified quantitative testing for plasma LAAR concentrations can now assist health care providers in determining when to safely discontinue VK1 therapy. We present estimates of treatment duration required to reach safe concentrations (< =10ng/ml) using serial measurements of plasma brodifacoum (BDF, a potent LAAR) concentrations obtained from patients poisoned after inhaling synthetic cannabinoids containing BDF. We fit the data to zero-order (linear) and first-order (exponential) curves, the latter to account for enterohepatic circulation of BDF. The results show that estimates of therapy duration are significantly longer when exponential clearance is assumed. Accordingly, we recommend that plasma BDF concentrations be monitored simultaneously with international normalization ratio (INR) during follow-up of poisoned patients, and that concentrations be determined after VK1 therapy is discontinued to document persistence of safe concentrations.

The extent to which the last decade has yielded additional treatment options for EGFR-associated rash besides classic treatment with antibiotics and corticosteroids - A systematic review.

PURPOSE: To investigate the effectiveness of different interventions for the prevention and treatment of EGFRI treatment-induced rash (EGFRIr) that appeared in the last decade, excluding antibiotics and steroids products alone. METHOD: A systematic review was performed in 2019 and was updated in 2020. The search strategy was limited to studies published within the last 10 years on the Medline database accessed via Pubmed and the Cochrane database. The search was performed using keywords combined with AND, OR. RESULTS: The search yielded thirteen studies. The studies were divided into two categories, based on the intervention method used: four studies used creams containing vitamin K1 or vitamin K3 (henceforth classified as "Category A″) and nine studies ("Category B″) focused on different intervention methods such as laser treatment, Polydatin (PD) cream treatment, treatment with sunscreen, Adapalene gel treatment, topical aloe vera treatment, topical hydration treatment, the impact of a pre-emptive skin treatment and, finally, epidermal growth factor (EGF) ointment treatment. From "Category A″, the results vary as two studies found no benefit from cream use, while two studies indicated a possible improvement on skin reactions from cream use. In "Category B″, a benefit due to laser treatment was indicated, Polydatin-containing moisturizer showed a reduction in the incidence of rash grade ≥ II in patients treated with afatinib, while treatment with sunscreen demonstrated no benefit for the prevention of EGFRIr. Additionally, Adapalene gel use is not recommended as prophylaxis for EGFRIr, topical aloe vera may be used in the management for EGFRIr due to cetuximab, topical hydration resolved the EFGRIr, the pre-emptive skin treatment routine was well tolerated and the epidermal growth factor ointment improved all the symptoms due to EGFRI. CONCLUSIONS: The results from the studies vary, although this study focuses on reviewing treatment interventions that can be utilized, apart from antibiotics and steroids, in order to alleviate the problems of the patients suffering from EGFRIr. More specifically, the authors of this review cannot draw a conclusion from "Category A″, as the efficacy of vitamin K for the management of EGFRIr is controversial. From "Category B″, some of the suggested treatments show encouraging results, while others may prove ineffective and rather harmful for the patients.

Vitamin K2 Needs an RDI Separate from Vitamin K1.

Vitamin K and its essential role in coagulation (vitamin K [Koagulation]) have been well established and accepted the world over. Many countries have a Recommended Daily Intake (RDI) for vitamin K based on early research, and its necessary role in the activation of vitamin K-dependent coagulation proteins is known. In the past few decades, the role of vitamin K-dependent proteins in processes beyond coagulation has been discovered. Various isoforms of vitamin K have been identified, and vitamin K2 specifically has been highlighted for its long half-life and extrahepatic activity, whereas the dietary form vitamin K1 has a shorter half-life. In this review, we highlight the specific activity of vitamin K2 based upon proposed frameworks necessary for a bioactive substance to be recommended for an RDI. Vitamin K2 meets all these criteria and should be considered for a specific dietary recommendation intake.

Vitamin K-what is known regarding bariatric surgery patients: a systematic review.

Vitamin K, a fat-soluble vitamin, is involved in blood coagulation, bone mineralization, inhibition of vascular calcification, and regulation of numerous enzyme systems. Patients who undergo bariatric surgery (BS), especially procedures that involve a malabsorptive component, are prone to develop vitamin K deficiency (VKD). The causes of VKD include decreased absorptive surface areas, steatorrhea, bacterial overgrowth, marked reduction of carriers of vitamin K, decrease in vitamin K intake, and modifications of gut microbiota. Data on vitamin K status among BS patients are scarce and the strength of evidence supporting vitamin K supplementation is weak. Thus, this systematic review summarized the scientific literature on vitamin K and examined the status among patients before and after BS, as well as among pregnant women with a history of BS. A MEDLINE/Pubmed and Embase electronic search was performed. After a thorough screening of 204 titles, 19 articles were selected by 2 independent reviewers. Five studies on BS candidates (n = 750), 12 studies after BS (n = 1442), and 4 studies on pregnant woman after BS (n = 83, of them n = 7 from case reports) were included. Results of the current review suggest that patients who undergo major malabsorptive surgeries are at a higher risk of developing VKD and should be better monitored. At this point, it is still unclear whether supplementation of vitamin K is required, and what oral dose or vitamer type should be used to normalize serum levels after different types of bariatric procedures. It should be noted that the current protocols for VKD treatment are still experiential in these patients. It is also unknown at what intervals screening tests for vitamin K should be performed and what assay is most appropriate for screening purposes. Future studies are needed to answer these unresolved issues.

Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease.

Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures, namely, phylloquinone (K1) and menaquinones (K2). The difference in structure between K1 and K2 is seen in different absorption rates, tissue distribution, and bioavailability. Although differing in structure, both act as cofactor for the enzyme gamma-glutamylcarboxylase, encompassing both hepatic and extrahepatic activity. Only carboxylated proteins are active and promote a health profile like hemostasis. Furthermore, vitamin K2 in the form of MK-7 has been shown to be a bioactive compound in regulating osteoporosis, atherosclerosis, cancer and inflammatory diseases without risk of negative side effects or overdosing. This review is the first to highlight differences between isoforms vitamin K1 and K2 by means of source, function, and extrahepatic activity.

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.

Application of a New Established System for Toxic Doses in Children With 4-Hydroxycoumarin Rodenticide Intoxication.

The toxic dose of rodenticides in children is extremely difficult to be determined because of the uncertain exposure history. We established and validated a method to identify the toxic dose in children of 4-hydroxycoumarin (TDCH). Items were selected by Delphi method and weighted by analytic hierarchy process. Toxic doses were classified into three categories: high dose (>24 points), medium (15-24) and low (<15). Sixty-five children with 4-hydroxycoumarin rodenticide intoxication were included in the study. There were 29(44.6%), 8(12.3%), 28(43.1%) cases in high, medium, and low dose respectively. Patients in high-dose were more likely to have intentionally attempted suicide (5/29, 17.2%) or had no definite history of ingestion (17/29, 58.6%), arrived at the hospital later than 24 h (26/29, 90%), been misdiagnosed initially (25/29, 86.2%), not treated by gastric lavage (27/29, 93.1%), and developed severe hemorrhage. While most patients in low-dose were younger than 6 years (26/28, 92.9%), all have experienced accidental exposure, arrived at the hospital, and received gastric lavage within 24 h, obtained a definite diagnosis, and be asymptomatic. Of 38 patients arrived at hospital within 48 h, patients a score48h ≥ 15 had higher incidence of coagulopathy (6/8, 75.0%) than patients with a score48h < 15 (3/30, 10.0%). Of all patients, 37 in the high and medium dose with a score ≥ 15 has higher incidence (35/37, 94.6%) of prolonged administration with vitamin K1 (≥1 month) than other 28 patients with a score < 15 (0/28, 0%). The TDCH system could not only be used in evaluating toxic doses and predicting coagulopathy in the early stage, but also helps to guide appropriate treatment. Patients with a score48h ≥ 15 were in the high bleeding risk category. And patients with a scores ≥ 15 required treatment with vitamin K1 for more than a month.

Development of a kelp powder (Thallus laminariae) Standard Reference Material.

A Standard Reference Material (SRM) of seaweed, SRM 3232 Kelp Powder (Thallus laminariae) has been developed to support food and dietary supplement measurements in compliance with the Food Safety Modernization Act (FSMA) and the Dietary Supplement Health and Education Act of 1994 (DSHEA). The material was characterized for nutritional minerals, arsenic species, isomers of vitamin K1, proximates, and toxic elements. Kelp is a rich source of vitamins and minerals, and it is an excellent source of dietary iodine. Kelp also contains a large amount of arsenic, which is toxic as inorganic species but much less so as organic species. To capture the dietary profile of kelp, certified values were issued for As, Ca, Cd, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Mo, Na, Pb, and Zn. Reference values for proximates were assigned. For the first time, a certified value for iodine, reference values for isomers of vitamin K1, and reference values for arsenic species including arsenosugars were assigned in a seaweed. SRM 3232 fills a gap in Certified Reference Materials (CRMs) needed for quality assurance and method validation in the compositional measurements of kelp and similar seaweeds used as food and as dietary supplements. Graphical Absract Arsenic species and isomers of vitamin K1 were determined in the development of SRM 3232 Kelp Powder (Thallus laminariae).

Vitamin K1 inversely correlates with glycemia and insulin resistance in patients with type 2 diabetes (T2D) and positively regulates SIRT1/AMPK pathway of glucose metabolism in liver of T2D mice and hepatocytes cultured in high glucose.

There is no previous study in the literature that has examined the relationship between circulating vitamin K1 (VK1) with glycemic status in type 2 diabetes (T2D). Moreover, scientific explanation for the beneficial role of VK1 supplementation in lowering glycemia in diabetes is yet to be determined. This study for the first time demonstrated that circulating VK1 was significantly lower in T2D patients compared to age-matched control subjects, and VK1 levels in T2D were significantly and inversely associated with fasting glucose and insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], which suggest that boosting plasma VK1 may reduce the fasting glucose and insulin resistance in T2D patients. Using high-fat-diet-fed T2D animal model, this study further investigated the positive effect of VK1 supplementation on glucose metabolism and examined the underlying molecular mechanism. Results showed that VK1 supplementation [1, 3, 5 µg/kg body weight (BW), 8 weeks] dose dependently improved the glucose tolerance; decreased BW gain, fasting glucose and insulin, glycated hemoglobin, HOMA-IR and cytokine secretion (monocyte chemoattractant protein-1 and interleukin-6); and regulated the signaling pathway of hepatic glucose metabolism [sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK)/phosphoinositide 3-kinase/phosphatase and tensin homolog/glucose transporter 2/glucokinase/glucose 6 phosphatase], lipid oxidation (peroxisome proliferator-activated receptor alpha/carnitine palmitoyltransferase 1A) and inflammation (nuclear factor kappa B) in T2D mice. Comparative signal silencing studies also depicted the role of SIRT1/AMPK in mediating the effect of VK1 on glucose metabolism, lipid oxidation and inflammation in high-glucose-treated cultured hepatocytes. In conclusion, this study demonstrates that circulating VK1 has a positive effect on lowering fasting glucose and insulin resistance in T2D via regulating SIRT1/AMPK signaling pathway.