Effects of radical scavengers for reactive oxygen species on vitamin K-induced phototoxicity under UVA irradiation.

Vitamin K possesses efficacy as a topical dermatological agent. However, vitamin K is phototoxic and susceptible to photodegradation. Herein, we investigated the mechanisms underlying the phototoxicity of phylloquinone (PK, vitamin K1) and menaquinone-4 (MK-4, vitamin K2) under ultraviolet A (UVA) irradiation using various reactive oxygen species (ROS) scavengers. This resulted in the production of superoxide anion radicals via type I and singlet oxygen via type II photodynamic reactions, which were quenched by the ROS scavengers: superoxide dismutase and sodium azide (NaN3). In HaCaT cells, MK-4 and PK induced the production of intracellular ROS, particularly hydrogen peroxide, in response to UVA irradiation. Furthermore, the addition of catalase successfully decreased maximum ROS levels by approximately 30%. NaN3 and catalase decreased the maximum reduction in cell viability induced by UVA-irradiated PK and MK-4 in cell viability by approximately 2-7-fold. Additionally, ROS scavengers had no effect on the photodegradation of PK or MK-4 at 373 nm. Therefore, the phototoxicities of PK and MK-4 were attributed to the generation of singlet oxygen and hydrogen peroxide, underscoring the importance of photoshielding in circumventing phototoxicity.

Vitamin K content of Australian-grown horticultural commodities.

Vitamin K is a multi-function vitamin that has emerging roles in bone, brain and vascular health. Vitamin K composition data remain limited globally and Australia has lacked nationally representative data for vitamin K1 (phylloquinone) in horticultural commodities. Primary samples (n = 927) of 90 Australian-grown fruit, vegetable and nut commodities were purchased in three Australian cities. We measured vitamin K1/phylloquinone in duplicate in 95 composite samples using liquid chromatography with electrospray ionisation-tandem mass spectrometry. The greatest mean concentrations of vitamin K1/phylloquinone were found in kale (565 µg/100 g), baby spinach (255 µg/100 g) and Brussels sprouts (195 µg/100 g). The data contribute to the global collection of vitamin K food composition data. They add to the evidence that vitamin K1/phylloquinone concentrations vary markedly between geographic regions, supporting development of region-specific datasets for national food composition databases that do not yet contain data for vitamin K. Such data are needed globally.

Vitamin K1 intake is associated with lower risk for all-cause and cardiovascular disease mortality in community-dwelling older Australian women.

BACKGROUND AND AIMS: Assessing the relationship between vitamin K1 intakes, using region-specific food databases, with both all-cause, and cardiovascular disease (CVD) mortality warrants further investigation to inform future preventative strategies. Consequently, we examined the aforementioned associations in the Perth Longitudinal Study of Ageing Women (PLSAW). METHODS AND RESULTS: 1436 community-dwelling older Australian women (mean ± SD age 75.2 ± 2.7 years) completed a validated food frequency questionnaire at baseline (1998). Vitamin K1 intake was calculated based on an Australian vitamin K food database, supplemented with published data. All-cause and CVD mortality data was obtained from linked health records. Associations were examined using restricted cubic splines within Cox-proportional hazard models, adjusted for a range of cardiovascular and lifestyle related risk factors. Over 15 years of follow-up, 601 (41.9%) women died, with 236 deaths (16.4%) due to CVD. Compared to women with the lowest vitamin K1 intakes (Quartile 1, median 49.1 µg/day), those with the highest intakes (Quartile 4, median 119.3 µg/day) had lower relative hazards for all-cause mortality (HR 0.66 95%CI 0.51-0.86) and CVD mortality (HR 0.61 95%CI 0.41-0.92). A plateau in the inverse association was observed from vitamin K1 intakes of approximately ≥80 µg/day. CONCLUSION: Higher vitamin K1 intakes were associated with lower risk for both all-cause and CVD mortality in community-dwelling older women, independent of CVD related risk factors. A higher intake of vitamin K1 rich foods, such as leafy green vegetables, may support cardiovascular health.

A Negative Association between Plasma Phylloquinone and All-Cause Mortality in Chinese Adults with Hypertension: A Nested Case-Control Study.

BACKGROUND: Previous studies have revealed that vitamin K is essential for preventing various chronic diseases. Phylloquinone is the primary dietary and circulating form of vitamin K. However, data concerning the association between plasma phylloquinone and all-cause mortality are limited. OBJECTIVES: This study aimed to evaluate the association between plasma phylloquinone and risk of all-cause mortality and examine some potential confounders. METHODS: This study is a post hoc analysis of the RCT and a nested, case-control design was used. Enrolled participants had to have hypertension at baseline. Study initiation was 19 May, 2008, and the median follow-up was 4.5 y. A total of 604 mortality cases and 604 controls matched for age, sex, treatment group, and study site were included in this study. Odds ratios (OR) and 95% confidence intervals (CIs) of all-cause mortality were calculated using conditional or unconditional logistic regression, without or with adjusting for pertinent covariates, respectively. The concentration of phylloquinone was measured by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). RESULTS: The mean and median phylloquinone levels were 1.62 nmol/L and 0.89 nmol/L, respectively. There was a significant negative association between log-transformed plasma phylloquinone and all-cause mortality after controlling for potential confounders (per 1 unit increase-OR: 0.79; 95% CI: 0.66, 0.95). Furthermore, the association of plasma phylloquinone with risk of all-cause mortality differed by body mass index (BMI) (<25 kg/m2 compared with ≥25 kg/m2, P-interaction = 0.004). A significant trend of decreasing risk with increasing concentration of phylloquinone was observed in participants with higher BMI (per 1 unit increase-OR: 0.71; 95% CI: 0.56, 0.90; P = 0.004). No significant correlation was found between phylloquinone and risk of all-cause mortality in those with BMI <25 kg/m2. CONCLUSIONS: In Chinese patients with hypertension, there was a significant negative association between baseline plasma phylloquinone and all-cause mortality, especially among those with higher BMI.

Analysis of vitamin K1 and major K2 variants in rat/human serum and lipoprotein fractions by a rapid, simple, and sensitive UHPLC-MS/MS method.

Determination of the various forms of vitamin K, which are involved in coagulation and other physiological processes in humans, is challenging and no standardized method is yet available. Therefore, a reliable and practical method was developed to quantify vitamin K levels in serum and additionally in lipoprotein fractions to clarify its distribution. The LC-MS/MS method for the determination of vitamin K1 and the three main isoforms of vitamin K2 (MK-4, MK-7, MK-9) was combined with a gradient ultracentrifugation technique to allow the separation of lipoprotein fractions. The chromatographic separation was carried out on a Kinetex™ C18 column using a mobile phase consisting mainly of methanol. The target analytes were detected by electrospray ionization mass spectrometry. The separation of all four substances was achieved after a simple sample preparation technique based on miniaturized liquid-liquid extraction. Our method of only 8.5 min revealed the levels of the major forms of vitamin K in 59 human and 12 rat sera and confirmed our hypothesis that vitamin K is primarily (about 50 %) found in the high-density lipoprotein fraction. The median concentrations of vitamin K1, MK-4, MK-7, and MK-9 were found to be 1.19, 2.98, 0.43, and < 0.71 nmol/L in human serum and 1.74, 6.75, less than 0.2, and less than 0.5 nmol/L in rat serum, respectively.

Vitamin K - a scoping review for Nordic Nutrition Recommendations 2023.

Vitamin K occurs in dietary supply in two major forms: phylloquinone (vitamin K1) and menaquinones (collectively referred as vitamin K2). Phylloquinone is derived from plants. There are at least 10 forms of menaquinones varying in chain length and they are produced by bacteria except menaquinone-4. Menaquinone-4 is formed from phylloquinone or other menaquinone forms. Phylloquinone is considered to be the major contributor and menaquinones are thought to contribute less to vitamin K intake in Western diets. However, less is known about the content of menaquinones than phylloquinones in foods. Vitamin K is known to function as an enzymatic cofactor in the gamma-carboxylation of vitamin K dependent proteins (VKDPs). Hepatic VKDPs are involved in coagulation. Extrahepatic VKDPs have a role e.g. in bone health and vascular calcification. However, the amount of vitamin K needed for optimal functioning of the different VKDPs is not known.

Phylloquinone is preferable over menadione as a growth factor for Porphyromonas gingivalis.

OBJECTIVES: Porphyromonas gingivalis is the etiological agent of chronic periodontitis. Menadione (vitamin K3) and phylloquinone (vitamin K1) are well-known growth factors for P. gingivalis, while menadione is widely used in growth experiments. Here we attempted to determine the differences in phylloquinone and menadione in P. gingivalis growth experiments, which have not been well studied to date. METHODS: We investigated the effects of menadione and phylloquinone on the growth of two W83 strains and seven ATCC 33277 strains of P. gingivalis. RESULTS: The ATCC 33277 strains grew well with phylloquinone at 2.9 µM in a complex medium (nutrient medium) and at 29 µM in two minimal media. In contrast, the W83 strains grew well without menadione or phylloquinone in three different culture media. Menadione at 2.9 µM, the conventionally used concentration for culturing P. gingivalis, supported the growth of most ATCC 33277 strains but inhibited the growth of some W83 and ATCC 33277 strains. Furthermore, menadione at 14.5 µM frequently inhibited cell growth, while phylloquinone at 145 µM promoted cell growth. CONCLUSIONS: These results indicate that menadione and phylloquinone act as growth factors for ATCC 33277 but that menadione also can inhibit P. gingivalis growth. Thus, we propose that phylloquinone be used instead of menadione in P. gingivalis growth experiments requiring vitamin K.

Time-resolved FTIR difference spectroscopy for the study of photosystem I with high potential naphthoquinones incorporated into the A1 binding site 2: Identification of neutral state quinone bands.

Time-resolved step-scan FTIR difference spectroscopy at 77 K has been used to study photosystem I (PSI) from Synechocystis sp. PCC 6803 with four high-potential, 1,4-naphthoquinones (NQs) incorporated into the A1 binding site. The incorporated quinones are 2-chloro-NQ (2ClNQ), 2-bromo-NQ (2BrNQ), 2,3-dichloro-NQ (Cl2NQ), and 2,3-dibromo-NQ (Br2NQ). For completeness 2-methyl-NQ (2MNQ) was also incorporated and studied. Previously, PSI with the same quinones incorporated were studied in the, so-called, anion spectral region between 1550 and 1400 cm-1 (Agarwala et al. in Biochim Biophys Acta 1864(1):148918, 2023). Here we focus on spectra in the previously unexplored 1400-1200 cm-1 spectral region. In this region several bands are identified and assigned to the neutral state of the incorporated quinones. This is important as identification of neutral state quinone bands in the regular 1700-1600 cm-1 region has proven difficult in the past. For neutral PhQ in PSI a broad, intense band appears at ~ 1300 cm-1. For the symmetric di-substituted NQs (Cl2NQ/Br2NQ) a single intense neutral state band is found at ~ 1280/1269 cm-1, respectively. For both mono-substituted NQs, 2ClNQ and 2BrNQ, however, two neutral state bands are observed at ~ 1280 and ~ 1250 cm-1, respectively. These observations from time-resolved spectra agree well with conclusions drawn from absorption spectra of the NQs in THF, which are also presented here. Density functional theory based vibrational frequency calculations were undertaken allowing an identification of the normal modes associated with the neutral state quinone bands.

Lack of Consensus Between Measurements of Plasma Phylloquinone by Enzyme-Linked Immunosorbent assays and a Well-Validated High-Performance Liquid Chromatographic Method.

Enzyme-linked i2mmunosorbent assays (ELISAs) that measure circulating phylloquinone have become commercially available, but their validity is uncertain. The objective of this study was to compare plasma phylloquinone concentrations measured using two commercially available ELISAs with concentrations measured using a validated high-performance liquid chromatography (HPLC) assay in 108 samples obtained from participants in a depletion (∼10 mcg phylloquinone/d)-supplementation (∼500 mcg phylloquinone/d) study. The geometric mean of plasma phylloquinone measured with ELISA A was 0.70 nmol/L, 37% lower than that measured with HPLC. The mean of the ELISA B measures was 12.4 nmol/L, >700% higher than the HPLC measures. Plasma phylloquinone measured using HPLC was significantly lower during phylloquinone depletion than supplementation (0.4 ± 0.1 compared with 1.2 ± 0.2 nmol/L; P < 0.001). Neither of the two ELISAs detected any significant difference in plasma phylloquinone concentrations between depletion and supplementation (ELISA A, P = 0.76; ELISA B, P = 0.29). These findings reinforce the need to validate plasma phylloquinone assays as they become available. Curr Dev Nutr 2023;x:xx.

Measurement of vitamin K and its derivatives in human plasma through enzyme-assisted liquid chromatography-tandem mass spectrometry assay.

Vitamin K is an essential lipophilic vitamin that acts as a coenzyme in several metabolic pathways. Accurate measurement of apolar metabolites transported by lipoproteins in serum matrices requires high-recovery extractions of vitamin K and its derivatives following standardized protocols. Conventionally developed methods in this field have predominantly employed solid-phase extraction for the measurement of vitamin K and its derivatives. In this study, our objective was to develop an enzyme-assisted extraction method for the precise measurement of vitamin K and its derivatives. Our methodology involved mixing 450 µL of serum samples with 50 µL of an internal standard and 50 µL of a lipase enzyme solution. Following vortexing, the mixture was incubated at 37°C for 15 min to activate the enzymes. The enzyme reaction was subsequently quenched with a mixture of 250 µL of methanol and 1 mL of hexane, followed by centrifugation at 12,000 g for 5 min. The upper phase was collected, concentrated using a concentrator device, and dissolved in a 100 µL solution of methanol/acetone/isopropanol (7:1:1, v/v/v) for analysis. Spectrum analysis was performed using the open-source MZmine 3 software, and a reference interval was established using the Python programming language on the Google Colab platform. The developed method for measuring vitamin K and its derivatives exhibited limit of detection and limit of quantitation values of 0.005 and 0.01 ng/mL, respectively. In conclusion, our study presents a precise and reliable method for the measurement of vitamin K and its derivatives using enzyme-assisted extraction.

Vitamin K1 Intake and Incident Diabetes in the Danish Diet, Cancer, and Health Study.

CONTEXT: Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors. OBJECTIVE: To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes. METHODS: Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes was determined using multivariable-adjusted Cox proportional-hazards models. RESULTS: In 54 787 Danish residents with a median (interquartile range) age of 56 (52-60) years at baseline, 6700 individuals were diagnosed with diabetes during 20.8 (17.3-21.6) years of follow-up. Vitamin K1 intake was inversely and linearly associated with incident diabetes (P < .0001). Compared to participants with the lowest vitamin K1 intake (median:57 µg/d), participants with the highest intakes (median:191 µg/d) had a 31% lower risk of diabetes (HR; 95% CI, 0.69; 0.64-0.74) after multivariable adjustments. The inverse association between vitamin K1 intake and incident diabetes was present in all subgroups (namely, men and women, ever and never smokers, low and high physical activity groups, and in participants who were normal to overweight and obese), with differences in absolute risk between subgroups. CONCLUSION: Higher intake of foods rich in vitamin K1 was associated with a lower risk of diabetes. If the associations observed are causal, our results indicate that more cases of diabetes would be prevented in subgroups at higher risk (men, smokers, participants with obesity, and those with low physical activity).

Effect of phylloquinone on indomethacin-induced gastric ulceration in rats: Role of SIRT-1.

Gastric ulcer is the most common gastrointestinal disorder affecting people globally. Although many drugs are available to treat ulcers, the mortality rate is relatively high, and drugs lack selectivity to treat ulcers without causing side effects. In this study, the potential therapeutic effects of phylloquinone were tested against indomethacin-induced gastric ulcer in rats by giving rats a single oral dose of indomethacin (48 mg/kg), followed by phylloquinone (10 mg/kg) orally, once daily for six consecutive days. Phylloquinone significantly attenuated indomethacin-induced oxidative and inflammatory responses through hindering the inflammatory cascade by decreasing the levels of TNF-α, NF-κB, INOS and COX-2 which counteracts indomethacin effects. Also, it increased NAD+ which enhanced SIRT-1 level. Furthermore, phylloquinone was effective in increasing mucus secretion, decreasing acid secretion, reversing histological effects caused by indomethacin and minimizing ulcer and lesion indices All these findings indicate that phylloquinone may be used in protection and treatment of indomethacin-induced gastric ulcer.

Higher Dietary Vitamin K Intake is Associated with Better Physical Function and Lower Long-Term Injurious Falls Risk in Community-Dwelling Older Women.

BACKGROUND: In recent years, a potential beneficial role of Vitamin K in neuromuscular function has been recognised. However, the optimal dietary intake of Vitamin K to support muscle function in the context of falls prevention remains unknown. OBJECTIVE: To examine the relationship of dietary Vitamin K1 and K2 with muscle function and long-term injurious fall-related hospitalisations in older women. DESIGN: Cohort study. PARTICIPANTS: 1347 community-dwelling older Australian women ≥70 years. MEASUREMENTS: A new Australian Vitamin K nutrient database, supplemented with published data, was used to calculate Vitamin K1 and K2 intake from a validated food frequency questionnaire at baseline (1998). Muscle function (grip strength and timed-up-and-go; TUG) as well plasma Vitamin D status (25OHD) were also assessed at baseline. Fall-related hospitalisations over 14.5 years were obtained from linked health records. Multivariable-adjusted logistic regression and Cox-proportional hazard models were used to analyse the data. RESULTS: Over 14.5 years of follow-up (14,774 person-years), 535 (39.7%) women experienced a fall-related hospitalisation. Compared to women with the lowest Vitamin K1 intake (Quartile 1, median 49 µg/d), those with the highest intake (Quartile 4, median 120 µg/d) had 29% lower odds (OR 0.71 95%CI 0.52-0.97) for slow TUG performance (>10.2 s), and 26% lower relative hazards of a fall-related hospitalisation (HR 0.74 95%CI 0.59-0.93) after multivariable adjustment. These associations were non-linear and plateaued at moderate intakes of ~70-100 µg/d. There was no relation to grip strength. Vitamin K2 intakes were not associated with muscle function or falls. CONCLUSION: A higher habitual Vitamin K1 intake was associated with better physical function and lower long-term injurious falls risk in community-dwelling older women. In the context of musculoskeletal health, Vitamin K1 found abundantly in green leafy vegetables should be promoted.

Fat-soluble vitamin and phytochemical metabolites: Production, gastrointestinal absorption, and health effects.

Consumption of diets rich in fruits and vegetables, which provide some fat-soluble vitamins and many phytochemicals, is associated with a lower risk of developing certain degenerative diseases. It is well accepted that not only the parent compounds, but also their derivatives formed upon enzymatic or nonenzymatic transformations, can produce protective biological effects. These derivatives can be formed during food storage, processing, or cooking. They can also be formed in the lumen of the upper digestive tract during digestion, or via metabolism by microbiota in the colon. This review compiles the known metabolites of fat-soluble vitamins and fat-soluble phytochemicals (FSV and FSP) that have been identified in food and in the human digestive tract, or could potentially be present based on the known reactivity of the parent compounds in normal or pathological conditions, or following surgical interventions of the digestive tract or consumption of xenobiotics known to impair lipid absorption. It also covers the very limited data available on the bioavailability (absorption, intestinal mucosa metabolism) and summarizes their effects on health. Notably, despite great interest in identifying bioactive derivatives of FSV and FSP, studying their absorption, and probing their putative health effects, much research remains to be conducted to understand and capitalize on the potential of these molecules to preserve health.

COVID-19-associated Coagulopathy: Role of Vitamins D and K.

Recent reports show coagulopathy as a potential complication and poorer outcome of coronavirus disease 2019 (COVID-19), especially in those with comorbid conditions such as diabetes and hypertension as thrombosis could result in stroke and heart attacks. Indeed, cardiovascular complications in COVID-19 account for 40% of mortality. Although there is no standard treatment protocol or guidelines for COVID-19, it is a common practice to use anti-inflammatory corticosteroids and anti-coagulants, especially for severe COVID-19 patients. It has also been confirmed that deficiencies of vitamin D and/or vitamin K can exacerbate premorbid cardiovascular and diabetes conditions associated with COVID-19, at least partially due to a higher incidence of coagulopathy. Here, we discuss the roles of vitamins D and K in general and in COVID-19-related coagulopathy. Moreover, the suggestion for proper supplementations of these vitamins in countering COVID-19 is provided.

Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible.

Proteins involved in fat-soluble vitamin and carotenoid transport across the intestinal cells: New insights from the past decade.

It is now well established that vitamins D, E, and K and carotenoids are not absorbed solely through passive diffusion. Broad-specificity membrane transporters such as SR-BI (scavenger receptor class B type I), CD36 (CD36 molecule), NPC1L1 (Niemann Pick C1-like 1) or ABCA1 (ATP-binding cassette A1) are involved in the uptake of these micronutrients from the lumen to the enterocyte cytosol and in their secretion into the bloodstream. Recently, the existence of efflux pathways from the enterocyte back to the lumen or from the bloodstream to the lumen, involving ABCB1 (P-glycoprotein/MDR1) or the ABCG5/ABCG8 complex, has also been evidenced for vitamins D and K. Surprisingly, no membrane proteins have been involved in dietary vitamin A uptake so far. After an overview of the metabolism of fat-soluble vitamins and carotenoids along the gastrointestinal tract (from the mouth to the colon where interactions with microbiota may occur), a focus is placed on the identified and candidate proteins participating in the apical uptake, intracellular transport, basolateral secretion and efflux back to the lumen of fat-soluble vitamins and carotenoids in enterocytes. This review also highlights the mechanisms that remain to be identified to fully unravel the pathways involved in fat-soluble vitamin and carotenoid intestinal absorption.

Time-resolved FTIR difference spectroscopy for the study of photosystem I with high potential naphthoquinones incorporated into the A1 binding site.

Time-resolved step-scan Fourier transform infrared difference spectroscopy has been used to study cyanobacterial photosystem I photosynthetic reaction centers from Synechocystis sp. PCC 6803 (S6803) with four high-potential, 1,4-naphthoquinones incorporated into the A1 binding site. The high-potential naphthoquinones are 2-chloro-, 2-bromo-, 2,3-dichloro- and 2,3-dibromo-1,4-naphthoquinone. "Foreign minus native" double difference spectra (DDS) were constructed by subtracting difference spectra for native photosystem I (with phylloquinone in the A1 binding site) from corresponding spectra obtained using photosystem I with the different quinones incorporated. To help assess and assign bands in the difference and double difference spectra, density functional theory based vibrational frequency calculations for the different quinones in solvent, or in the presence of a single asymmetric H- bond to either a water molecule or a peptide backbone NH group, were undertaken. Calculated and experimental spectra agree best for the peptide backbone asymmetrically H- bonded system. By comparing multiple sets of double difference spectra, several new bands for the native quinone (phylloquinone) are identified. By comparing calculated and experimental spectra we conclude that the mono-substituted halogenated NQs can occupy the binding site in either of two different orientations, with the chlorine or bromine atom being either ortho or meta to the H- bonded CO group.

Fish Microbiome Modulation and Convenient Storage of Aquafeeds When Supplemented with Vitamin K1.

Vitamin K (VK) is a fat-soluble vitamin necessary for fish metabolism and health. VK stability as dietary component during aquafeed storage and its potential effect on intestinal microbiome in fish have not yet been completely elucidated. The convenient storage conditions of aquafeeds when supplemented with phylloquinone (VK1), as well as its potential effects on the gut microbiota of Senegalese sole (Solea senegalensis) juveniles, have been explored. Experimental feeds were formulated to contain 0, 250 and 1250 mg kg-1 of VK1 and were stored at different temperatures (4, -20 or -80 °C). VK stability was superior at -20 °C for short-term (7 days) storage, while storing at -80 °C was best suited for long-term storage (up to 3 months). A comparison of bacterial communities from Senegalese sole fed diets containing 0 or 1250 mg kg-1 of VK1 showed that VK1 supplementation decreased the abundance of the Vibrio, Pseudoalteromonas, and Rhodobacterace families. All these microorganisms were previously associated with poor health status in aquatic organisms. These results contribute not only to a greater understanding of the physiological effects of vitamin K, particularly through fish intestinal microbiome, but also establish practical guidelines in the industry for proper aquafeed storage when supplemented with VK1.

Treatment of Vitamin K Deficiency in Hemodialysis Patients - A Pilot Study Comparing Menaquinone-7 Tablets and a Vitamin K Rich Diet.

Purpose: Vitamin K deficiency and hence a high level of plasma dephosphorylated undercarboxylated matrix Gla protein (dp-ucMGP) is frequent in patients on hemodialysis. This group is recommended to restrict their potassium intake which often leads to restriction of vitamin K rich foods. A menaquinone-7 (MK-7) supplement has been shown to decrease dp-ucMGP, but it has yet to be examined if a vitamin K rich diet could be equally effective. Patients and Methods: A prospective randomized crossover intervention trial with two arms; 6 weeks of 360 µg MK-7 tablet/day and 6 weeks of a vitamin K rich diet with a 3-week washout period in between. Participants were 10 patients in hemodialysis and the primary outcome measures were changes in dp-ucMGP, total MGP (tMGP), and undercarboxylated osteocalcin (ucOC). Furthermore, the level of potassium and phylloquinone in broccoli was determined after different durations of boiling. Results: During the MK-7 intervention the dp-ucMGP and ucOC decreased significantly compared to baseline (-0.42 [-0.93; -0.22] nmol/L (p=<0.01) and -1.85 [-2.91; -1.30] nmol/L (p<0.01)), while these were unchanged during the dietary intervention (0.03 [-0.64; 0.37] nmol/L (p=1.00) and 0.30 [-1.71; 1.41] nmol/L (p=0.77)). Between the two interventions there was a greater decrease in ucOC (p=0.02) during the MK-7 compared to the dietary period. No significant changes in the total MGP levels were found in any of the periods. The retention of potassium following boiling for 2 minutes and 8 minutes was 76% and 49%, respectively, while for phylloquinone the retention was 92%, and independent of duration of boiling. Conclusion: A daily MK-7 supplement for 6 weeks lowered dp-ucMGP and ucOC significantly, while a vitamin K rich diet was not able to induce any significant effect. Boiled broccoli maintains a reasonable content of phylloquinone while potassium is extracted and is a reasonable source of phylloquinone for patients on hemodialysis.