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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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Vitamin K is one of the most important fat-soluble vitamins. • Non-covalent interactions and quantum chemical properties are investigated theoretically. • ADME and Molecular Docking analyzes were performed. Vitamin K is one of the most important fat-soluble vitamins and while there are two main types of vitamin K in nature, known as K1 (phylloquinone) and K2 (menaquinones), there is also a synthetic type of vitamin K known as K3 (menadione). Recent studies have shown that it is crucial to know the non-covalent interactions, ADME and molecular docking of molecules in different solvent media. Therefore, we have performed some quantum chemical calculations, ADME and intra-and intermolecular interaction calculations of a number of K1, K2 and K3 such as K1-water (K1 + W), K1-methanol (K1 + M), K1-triacetin (K1 + T), K2-water (K2 + W), K2-methanol (K2 + M), K2-triacetin (K2 + T), K3-water (K3 + W), K3-methanol (K3 + M), K3-triacetin (K3 + T) performed by Density Functional Theory (DFT) and Multiwfn: A multifunctional wavefunction analyzer. Molecular structures, HOMO-LUMO energies, MEP and electronic properties have been calculated and described using DFT at the level of B3LYP/6-311G (d,p) level. The nature of the molecular interactions between vitamin K and solvents such as water, methanol and triacetin were also investigated using topological analyses such as atoms in molecule (AIM), non-covalent interaction index (NCI), reduced density gradient (RDG), Localized orbital locator (LOL) and electron localization function (ELF). In addition, FMO for electronic transitions, MEP for electrophilic and nucleophilic attack, ADME to investigate how a chemical is processed by a living organism, and Fukui functions to determine electron density are explained. Finally, molecular docking was used to determine the biological activity of the vitamin K. [ABSTRACT FROM AUTHOR]

The aim of the study was to estimate the content of K1, K2 (MK-n) as well as total K vitamins and their sources in the diets of 1985 PURE Poland study participants based on the FFQ questionnaire. Due to the pleiotropic effect of K vitamins, it is important to know their food sources depending on different eating habits. Total vitamin K in the diets amounted to 331.1 ± 151.5 µg/d and 358.6 ± 181.0 µg/d for men and women, respectively. Dietary patterns (DPs) were identified in the study group, and the relationship between them and vitamin K intake was assessed. The proportion of dominant products as sources of vitamin K in the fourth quartile of each of the three identified DPs did not change significantly compared to the proportion of these products as sources of vitamin K in all subjects. In the fourth quartile of individual DPs, vitamin K1 came mainly from vegetables (56.5–76.8%); K2 mainly from processed meat and high-fat cheese and cream (70.1–77.6%); and total K mainly from vegetables and processed meat (57.6–67.8%). Intakes of K vitamins were high and similar in terms of predominant vitamin K provider products, in groups of subjects whose diets were most consistent with the particular DP. In the absence of global findings on the most appropriate dietary content of MK-n vitamins other than phylloquinone, the estimated high content of these vitamins in the diets of the subjects compared with other nations suggests that their level in diets was satisfactory. Future studies should aim to determine the need for MK-n vitamins in terms of fulfilling all their functions in the body. [ABSTRACT FROM AUTHOR]

n the past, vitamin K was only known as a vitamin that plays a role in the production of coagulation factors and has been a neglected vitamin because its deficiency was rarely encountered. However, recent studies have shown that vitamin K2 plays an important role in building healthy bones, preventing bone resorption, protecting heart health, and even having a protective effect against various cancers such as lung, liver and prostate. More importantly, studies have shown that vitamin K2 is effective even on COVID-19, which causes mass deaths by affecting the whole world. In this study, vitamin K2 content of dairy products such as cheese, milk, yogurt, eggs, kefir, butter and margarine was determined by high performance liquid chromatography (HPLC). The highest total vitamin K2 contents were found in weave (503.40 ng g-1), cara (487.94 ng g-1) and crushing (439.19 ng g-1) cheese. Then, optimum conditions were determined to increase the vitamin K2 content of cheeses. [ABSTRACT FROM AUTHOR]

Vitamin K deficiency is evident in severe and fatal COVID-19 patients. It is associated with the cytokine storm, thrombotic complications, multiple organ damage, and high mortality, suggesting a key role of vitamin K in the pathology of COVID-19. To support this view, we summarized findings reported from machine learning studies, molecular simulation, and human studies on the association between vitamin K and SARS-CoV-2. We also investigated the literature for the association between vitamin K antagonists (VKA) and the prognosis of COVID-19. In addition, we speculated that fermented milk fortified with bee honey as a natural source of vitamin K and probiotics may protect against COVID-19 and its severity. The results reported by several studies emphasize vitamin K deficiency in COVID-19 and related complications. However, the literature on the role of VKA and other oral anticoagulants in COVID-19 is controversial: some studies report reductions in (intensive care unit admission, mechanical ventilation, and mortality), others report no effect on mortality, while some studies report higher mortality among patients on chronic oral anticoagulants, including VKA. Supplementing fermented milk with honey increases milk peptides, bacterial vitamin K production, and compounds that act as potent antioxidants: phenols, sulforaphane, and metabolites of lactobacilli. Lactobacilli are probiotic bacteria that are suggested to interfere with various aspects of COVID-19 infection ranging from receptor binding to metabolic pathways involved in disease prognosis. Thus, fermented milk that contains natural honey may be a dietary manipulation capable of correcting nutritional and immune deficiencies that predispose to and aggravate COVID-19. Empirical studies are warranted to investigate the benefits of these compounds. [ABSTRACT FROM AUTHOR]

No epidemiologic studies have been conducted to assess the association of intake of dietary vitamin K with the risk of pancreatic cancer. We used prospective data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial between 1993 and 2009 to fill this gap. A total of 101,695 subjects were identified. Dietary intakes of phylloquinone (vitamin K1), menaquinones (vitamin K2), and dihydrophylloquinone (dihydrovitamin K1) were assessed using a food frequency questionnaire. Cox regression was applied to calculate hazard ratios and 95% confidence intervals. During a mean follow-up of 8.86 years (900,744.57 person-years), 361 cases of pancreatic cancer were documented. In the fully adjusted model, dietary intakes of phylloquinone (for quartile 4 vs. quartile 1, hazard ratio (HR) = 0.57, 95% confidence interval (CI): 0.39, 0.83; P for trend = 0.002) and dihydrophylloquinone (for quartile 4 vs. quartile 1, HR = 0.59; 95% CI: 0.41, 0.85; P for trend = 0.006), but not menaquinones (for quartile 4 vs. quartile 1, HR = 0.93; 95% CI: 0.65, 1.33; P for trend = 0.816), were found to be inversely associated with the risk of pancreatic cancer in a nonlinear dose–response manner (all P values for nonlinearity < 0.05), and this was not modified by predefined stratification factors and remained in sensitivity analyses. In conclusion, dietary intakes of phylloquinone and dihydrophylloquinone, but not menaquinones, confer a lower risk of pancreatic cancer. Future studies should confirm our findings. [ABSTRACT FROM AUTHOR]

Several bacterial species associated with the human gut and with fermented foods produce menaquinones (MK-n; vitamin K2) as part of their energy metabolism. Given that MK-n offer multiple health benefits to humans, research into this topic is of increasing interest. To outline the current understanding of bacterial MK-n production and how it relates to the gut microbiota, food fermentation, the production of dietary supplements, and health. In bacteria, MK-n display various functions in addition to their chief role in energy production, including a role in defense mechanisms, the sensing of environmental changes, the reduction of metals, sporulation, and pathogenicity. In humans, they are relevant for health beyond the effects of phylloquinones (vitamin K1), which are primarily related to blood coagulation, as they seem to be more effective extrahepatically, impacting on cardiovascular and bone health and protecting against non-communicable diseases. While the contribution of gut microbiota to the human vitamin K budget remains unclear, more is known about fermented foods. Some fermented foods from either plant (e.g., sauerkraut and natto) or animal origin (e.g., cheese) are valuable sources of MK-n, even compared to non-fermented animal source foods, which only contain limited amounts of one specific form (MK-4). Bacillus subtilis , commonly used in the production of natto, is the most employed microorganism at industrial level for the production of dietary MK-7 supplements, a process which can be optimized by selecting the appropriate fermentation parameters. • In bacteria, MK-n have various functions in addition to their chief role in energy production. • In humans, vitamin K2 exerts various health-related benefits, broader so than K1. • The contribution of gut bacteria to vitamin K2 intake is less clear than for fermented foods. • Based on the bacteria involved, fermented foods provide different vitamin K2 forms. • Bacillus subtilis is used for the industrial production of dietary MK-7 supplements. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) infection is closely associated with gastrointestinal diseases. Our preliminary studies have indicated that H. pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer (GU) or duodenal ulcer (DU)., Aim: To investigate the contributions of H . pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases., Methods: Patients with H . pylori infection and either GU or DU, and healthy individuals without H . pylori infection were included. Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing. The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed., Results: Compared with that in the healthy individuals, the gastric mucosal microbiota in the H . pylori -positive patients with GU was dominated by H . pylori , with significantly reduced biodiversity. The intergroup differential functions, which were enriched in the H . pylori -positive GU patients, were all derived from H . pylori , particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones. A significant enrichment of the uibE gene was detected in the synthesis pathway. There was no significant difference in microbial diversity between the H. pylori -positive DU patients and healthy controls., Conclusion: H . pylori infection significantly alters the gastric microbiota structure, diversity, and biological functions, which may be important contributing factors for GU., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The acid–base and redox properties of the menaquinones MK-4, MK-7, and MK-9 (vitamin K2) have been studied in DMPC monolayers on mercury electrodes. The monolayers were prepared by adhesion-spreading of menaquinone-spiked DMPC liposomes on a stationary mercury drop electrode. All three menaquinones possess p K a constants outside the experimentally accessible range, i.e., they are higher than about 12. The standard potentials of MK-4, MK-7, and MK-9 in the DMPC monolayers are very similar, i.e., 0.351, 0.326, and 0.330 V (corresponding to the biochemical standard potentials − 0.063, − 0.088, and − 0.085 V). [ABSTRACT FROM AUTHOR]

• Four genera of thermophilic bacteria were analyzed. • Using off-line two-dimensional LC-tandem MS menaquinones (MK5) to MK15 were found. • A mixture of menaquinones having cis/trans double bond(s) was separated. Thermophilic bacteria of four genera in contrast to the commonly used production strains such as Bacillus subtilis , produce homologs other than menaquinone (MK) with seven isoprene units. The number of isoprene units and the configuration of double bonds are essential factors for their biological activity. The goal was to obtain a strain of bacteria that produces a wide range of MK homologs and only all- trans geometrical isomers, which was the strain G. kaustophilus. Using off-line two-dimensional LC–tandem MS in columns with the RP18 phase and the COSMOSIL cholester phase (separation according to the geometric configuration of double bonds) it was shown that thermophilic bacteria grown at different temperatures produce only all- trans isomers of menaquinones from MK-5 (menaquinone with five isoprenyl units) to MK-15 (fifteen isoprenyl units). Therefore, G. kaustophilus appears to be a biotechnologically important strain produces only trans isomers and additionally homologs from 5 to 15 isoprene units. [ABSTRACT FROM AUTHOR]

Vitamin K deficiency is evident in severe and fatal COVID-19 patients. It is associated with the cytokine storm, thrombotic complications, multiple organ damage, and high mortality, suggesting a key role of vitamin K in the pathology of COVID-19. To support this view, we summarized findings reported from machine learning studies, molecular simulation, and human studies on the association between vitamin K and SARS-CoV-2. We also investigated the literature for the association between vitamin K antagonists (VKA) and the prognosis of COVID-19. In addition, we speculated that fermented milk fortified with bee honey as a natural source of vitamin K and probiotics may protect against COVID-19 and its severity. The results reported by several studies emphasize vitamin K deficiency in COVID-19 and related complications. However, the literature on the role of VKA and other oral anticoagulants in COVID-19 is controversial: some studies report reductions in (intensive care unit admission, mechanical ventilation, and mortality), others report no effect on mortality, while some studies report higher mortality among patients on chronic oral anticoagulants, including VKA. Supplementing fermented milk with honey increases milk peptides, bacterial vitamin K production, and compounds that act as potent antioxidants: phenols, sulforaphane, and metabolites of lactobacilli. Lactobacilli are probiotic bacteria that are suggested to interfere with various aspects of COVID-19 infection ranging from receptor binding to metabolic pathways involved in disease prognosis. Thus, fermented milk that contains natural honey may be a dietary manipulation capable of correcting nutritional and immune deficiencies that predispose to and aggravate COVID-19. Empirical studies are warranted to investigate the benefits of these compounds.

Abstract Background The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors. Results By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an “induced” isolate formed a gradient of growth around a cultivatable “helper.” This set included two novel species Faecalibacterium sp. KLE1255—belonging to the anti-inflammatory Faecalibacterium genus—and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically. Conclusions Our data show that menaquinones are a major class of growth factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial growth media or modulate the human gut microbiota by encouraging the growth of important symbionts, such as Faecalibacterium species.

Vitamin K comes in several forms in foods. Phylloquinone (vitamin K1) is found in plant foods. Menaquinones (vitamin K2) are a class of vitamin K compounds found in animal products and fermented foods. The purpose of the research was to characterize the role of vitamins K1 and K2 in the nutrition of children and to assess vitamin K status in children. Material and methods . The literature review in recent years was carried out using the RSCI, Pubmed databases, as well as Google Scholar system using the keywords: «vitamin K», «vitamin K1», «vitamin K2», «menaquinone» and «phylloquinone» in combination with «children», or «breast milk». Results . Vitamins K1 and K2 are interchangeable in relation to the formation of blood coagulation factors, but the effectiveness of vitamin K2 is much higher in the posttranslational modification of extrahepatic proteins that provide antioxidant, epigenetic effects. Current vitamin K intake recommendations only apply to phylloquinone. Breastfed children are at risk for vitamin K deficiency, because breast milk content of vitamin K, mainly in the form of phylloquinone, is low. In adapted milk formulas for infant feeding, the content of vitamin K1 is significantly higher than in breast milk. To provide infants with vitamin K2, it is extremely important to promptly introduce complementary foods into the diet that are sources of menaquinones. Specifically formulated for the nutritional needs of young children products that contain naturally formed during milk fermentation vitamin K2, deserve special attention. Conclusion . Considering the important role of vitamin K in the prevention of the skeletal system and cardiovascular diseases, it is necessary to increase its consumption by including fermented foods naturally containing menaquinones (MK-7) in the diet., Competing Interests: The authors have no conflict of interest to declare., (Copyright© GEOTAR-Media Publishing Group.)

Aim: Differences are existed in the bioactivity among various vitamin K (VK) forms. To investigate the correlation between clinical parameters of initial anticoagulation and plasma levels of VK1 and VK2 (MK-4 and MK-7), it was necessary to establish a quantitative method for simultaneous determination. Materials & methods: Plasma samples in cardiovascular patients were extracted by cyclohexane and analyzed using a C18 column. Baseline concentrations of VK1, MK-4 and MK-7 were 0.98 ± 0.52 ng/ml, 0.45 ± 0.13 ng/ml and 0.65 ± 0.31 ng/ml, respectively. The concentrations of MK-7 and total VKs were significantly relevant to INR0, respectively (p = 0.010 and p = 0.048, respectively). Conclusion: Thus, when adjusting anticoagulation dosage, concentrations of various VK homologues might be considered.

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. • Major malabsorptive surgeries are a risk-factor to develop vitamin K deficiency. • The strength of evidence supporting pre-surgery vitamin K screening is weak. • The oral dose or vitamer type for post-surgery supplementation is uncertain. • The exact protocol for vitamin K deficiency treatment is still experiential. [ABSTRACT FROM AUTHOR]

Highlights • Summary of vitamin K analysis in various biological matrices. • This review collectively describes an updated overview of the sample pretreatment methodologies and methods for quantitative determination of vitamin K that have been used in last two decades. • LC–MS/MS detection of vitamin K will further help to evaluate the role of vitamin K in health and disease. Abstract Vitamin K is an essential nutrient in the body and involved in numerous physiological and pathophysiological functions. Both the lack and surplus of vitamin K can put human health at risk. Therefore, it becomes necessary to monitor vitamin K concentrations in different biomatrices through establishing sensitive and specific analytical methods. This review collectively describes an updated overview of the sample pretreatment methodologies and methods for quantitative determination of vitamin K that have been used in last two decades. High Performance Liquid Chromatography (HPLC) is commonly utilized as a standard for separation of vitamin K in combination with different detection including spectroscopic, spectrometric, fluorometric and mass spectroscopy. Recent progress in sample pretreatment technologies and quantitation methodologies have enhanced the ability to identify and quantitate vitamin K in biomatrices to further advance our understanding of the role of this vitamin in human health and disease. [ABSTRACT FROM AUTHOR]

Background: Menaquinone-4 (MK4), a vitamin K metabolite, is converted from phylloquinone through a process that requires intermediates of endogenous cholesterol production. Recent evidence suggests that MK4 is involved in kidney function.Objective: The purpose of this study was to determine the effect of atorvastatin treatment on MK4 formation in young and old male mice.Methods: C57BL/6 male mice (4-mo-old and 20-mo-old) were randomly assigned to either a diet containing 300 mg atorvastatin/kg with 3 mg phylloquinone/kg or a control diet containing 3 mg phylloquinone/kg for 8 wk. During week 8, all mice received deuterium-labeled phylloquinone in the diet. Labeled and unlabeled phylloquinone and MK4 in liver, kidney, brain, and intestine were measured by atmospheric pressure chemical ionization LC/MS. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene expression was quantified by reverse transcriptase-PCR. Tissue MK4 and phylloquinone concentrations were compared between atorvastatin treatment groups with use of general linear models.Results: There was no age-treatment interaction on MK4 tissue concentrations. In atorvastatin-treated mice, total MK4 and percentage of deuterium-labeled MK4 in kidney were both approximately 45% lower compared to values in mice not given atorvastatin (all P < 0.05). MK4 concentrations did not differ between groups in any other tissue measured.Conclusion: In male mice, atorvastatin reduced endogenous MK4 formation in the kidney, but not other organs. These observations are consistent with our hypothesis that cholesterol metabolism is involved in the generation of MK4. Further research is needed to understand potential regulatory mechanisms and the unique functions of MK4 in the kidney. [ABSTRACT FROM AUTHOR]

Our recent research indicated that honey active macromolecules form colloidal particles that scatter the light and produce elaborate UV spectral profile dominated by double absorption peaks at 240–250 nm. The absorption at 240–250 nm signified the stable honey conformation that supported antibacterial activity and hydrogen peroxide production. Our aim was to identify the bioactive constituent relevant to this absorption. The methodology included activity-guided fractionation of honey through size-exclusion chromatography, solid-phase extraction and UPLC-UV-MS. UV spectral analysis of UPLC peaks revealed compounds with UV λ (max) typical of naphtoquinones. The MS chromatograms showed mass ions differing by [M-68 n ] indicating a polyisoprene structure and the fragmentation patterns typical for menaquinones. The exact mass measurements of menaquinones using a quadrupole-Orbitrap mass spectrometry confirmed their identification as a series of MK-3 to MK-7 aptimers. Detection of menaquinones, previously unknown constituents of honey, suggests that they might play role in honey redox and antibacterial activities. [ABSTRACT FROM AUTHOR]

Background: Vitamin K2 (VK2) belongs to the vitamin K family and comprises a number of subtypes differing in length of side chains consisting of isoprenoid groups (menaquinone-n, MK-n). It is essential for a number of physiological functions although the full spectrum of activity has not yet been elucidated. Due to its role in protection of mitochondrial damage, VK2 could be relevant in preventing disease progress in multiple sclerosis (MS).Methods: We measured VK2 serum levels by the double antibody sandwich Enzyme-linked Immunosorbent Assay (ELISA) technique in MS patients and age and sex matched controls, both under vitamin D supplementation, and related it to disease characteristics and treatment.Results: Overall, 45 MS patients (31 females and 39 of the relapsing-remitting type) and 29 healthy controls (19 females) were included in the analysis. The MS patients had vastly lower VK2 blood levels than controls (235 ± 100 ng/ml vs. 812 ± 154 ng/ml, respectively). Female patients had significantly lower VK2 levels than males and a decrease with age by approximately 10% per decade was found. The VK2 levels were lower with increasing numbers of attacks per year and were higher in patients with optic nerve lesions. No consistent relationship with medications was detected.Conclusion: The substantially lower levels of VK2 in MS patients could be due to depletion, lower production in the gut, diminished absorption or, less likely, reduced intake of precursor vitamin K1. The role of VK2 in MS development and progress deserves further study. [ABSTRACT FROM AUTHOR]

Menaquinones (MK-n) can be produced by the fermentation of Flavobacterium meningosepticum . This article deals with the process of extraction, purification and identification of MK-4, MK-5 and MK-6. Among the organic solvents tested, the maximum extraction yields (99.1%) were obtained using three successive 20-min methanol extractions. Purification and separation of the menaquinone homologs, extracted from dry microbial cells with methanol, was achieved using adsorption chromatography, gel permeation chromatography and reverse-phase C18 chromatography on columns with large processing capacities (0.95–7.0 mg menaquinones per packing gram). The purities of MK-5 and MK-6 crystals reached 96.3% and 99.2%, respectively, as calculated by the external standard method. High recovery rates of 94.7% (not crystallized), 87.3% and 88.2% of MK-4, MK-5 and MK-6, respectively, were achieved for the overall process from extraction to crystallization. Throughout the entire process, the only organic solvents used were methanol and dichloromethane, facilitating the recycling of these solvents and, hence, application of the method on a large scale. The vitamin K 2 homologs were identified as MK-4, MK-5 and MK-6 by MS, IR and 1 H NMR. [ABSTRACT FROM AUTHOR]

Abstract Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for vitamin K. In this Opinion, the Panel considers vitamin K to comprise both phylloquinone and menaquinones. The Panel considers that none of the biomarkers of vitamin K intake or status is suitable by itself to derive DRVs for vitamin K. Several health outcomes possibly associated with vitamin K intake were also considered but data could not be used to establish DRVs. The Panel considers that average requirements and population reference intakes for vitamin K cannot be derived for adults, infants and children, and therefore sets adequate intakes (AIs). The Panel considers that available evidence on occurrence, absorption, function and content in the body or organs of menaquinones is insufficient, and, therefore, sets AIs for phylloquinone only. Having assessed additional evidence available since 1993 in particular related to biomarkers, intake data and the factorial approach, which all are associated with considerable uncertainties, the Panel maintains the reference value proposed by the Scientific Committee for Food (SCF) in 1993. An AI of 1 μg phylloquinone/kg body weight per day is set for all age and sex population groups. Considering the respective reference body weights, AIs for phylloquinone are set at 70 μg/day for all adults including pregnant and lactating women, at 10 μg/day for infants aged 7–11 months, and between 12 μg/day for children aged 1–3 years and 65 μg/day for children aged 15–17 years.

In contrast to other fat-soluble vitamins, dietary vitamin K is rapidly lost to the body resulting in comparatively low tissue stores. Deficiency is kept at bay by the ubiquity of vitamin K in the diet, synthesis by gut microflora in some species, and relatively low vitamin K cofactor requirements for γ-glutamyl carboxylation. However, as shown by fatal neonatal bleeding in mice that lack vitamin K epoxide reductase (VKOR), the low requirements are dependent on the ability of animals to regenerate vitamin K from its epoxide metabolite via the vitamin K cycle. The identification of the genes encoding VKOR and its paralog VKOR-like 1 (VKORL1) has accelerated understanding of the enzymology of this salvage pathway. In parallel, a novel human enzyme that participates in the cellular conversion of phylloquinone to menaquinone (MK)-4 was identified as UbiA prenyltransferase-containing domain 1 (UBIAD1). Recent studies suggest that side-chain cleavage of oral phylloquinone occurs in the intestine, and that menadione is a circulating precursor of tissue MK-4. The mechanisms and functions of vitamin K recycling and MK-4 synthesis have dominated advances made in vitamin K biochemistry over the last five years and, after a brief overview of general metabolism, are the main focuses of this review.

Summary Background & aims Vitamin K has been associated with various health outcomes, including non-fatal cardiovascular diseases (CVD) and cancer. However, little is known about the association between vitamin K intake and all-cause and cause specific mortality. This study aims to investigate the association between vitamin K intake and all-cause and cause-specific mortality. Methods This prospective cohort study included 33,289 participants from the EPIC-NL cohort, aged 20–70 years at baseline and recruited between 1993 and 1997. Dietary intake was assessed at baseline with a validated food frequency questionnaire and intakes of phylloquinone, and total, short chain and long chain menaquinones were calculated. Information on vital status and causes of death was obtained through linkage to several registries. The association between the different forms of vitamin K intake and mortality was assessed with Cox proportional hazards, adjusted for risk factors for chronic diseases and nutrient intake. Results During a mean follow-up of 16.8 years, 2863 deaths occurred, including 625 from CVD (256 from coronary heart disease (CHD)), 1346 from cancer and 892 from other causes. After multivariable adjustment, phylloquinone and menaquinones were not associated with all-cause mortality with hazard ratios for the upper vs. the lowest quartile of intake of 1.04 (0.92;1.17) and 0.94 (0.82;1.07) respectively. Neither phylloquinone intake nor menaquinone intake was associated with risk of CVD mortality. Higher intake of long chain menaquinones was borderline significantly associated (p trend = 0.06) with lower CHD mortality with a HR 10μg of 0.86 (0.74;1.00). None of the forms of vitamin K intake were associated with cancer mortality or mortality from other causes. Conclusions Vitamin K intake was not associated with all-cause mortality, cancer mortality and mortality from other causes. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined. Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation. Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8. Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation. Conclusion: Menaquinone concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear. This trial was registered at clinicaltrials.gov as NCT01902394. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for vitamin K. In this Opinion, the Panel considers vitamin K to comprise both phylloquinone and menaquinones. The Panel considers that none of the biomarkers of vitamin K intake or status is suitable by itself to derive DRVs for vitamin K. Several health outcomes possibly associated with vitamin K intake were also considered but data could not be used to establish DRVs. The Panel considers that average requirements and population reference intakes for vitamin K cannot be derived for adults, infants and children, and therefore sets adequate intakes (AIs). The Panel considers that available evidence on occurrence, absorption, function and content in the body or organs of menaquinones is insufficient, and, therefore, sets AIs for phylloquinone only. Having assessed additional evidence available since 1993 in particular related to biomarkers, intake data and the factorial approach, which all are associated with considerable uncertainties, the Panel maintains the reference value proposed by the Scientific Committee for Food (SCF) in 1993. An AI of 1 μg phylloquinone/kg body weight per day is set for all age and sex population groups. Considering the respective reference body weights, AIs for phylloquinone are set at 70 μg/day for all adults including pregnant and lactating women, at 10 μg/day for infants aged 7–11 months, and between 12 μg/day for children aged 1–3 years and 65 μg/day for children aged 15–17 years.This publication is linked to the following EFSA Supporting Publications article: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2017.EN-1220/full [ABSTRACT FROM AUTHOR]

Vitamin K is present in the diet in the forms of phylloquinone and menaquinones. Phylloquinone, which is the major dietary source, is concentrated in leafy plants and is the vitamin K form best characterized in terms of food composition and dietary intakes. In contrast, menaquinones are the product of bacterial production or conversion from dietary phylloquinone. Food composition databases are limited for menaquinones and their presence in foods varies by region. Dietary intakes of all forms of vitamin K vary widely among age groups and population subgroups. Similarly, the utilization of vitamin K from different forms and food sources appear to vary, although our understanding of vitamin K is still rudimentary in light of new developments regarding the menaquinones.

Subclasses of vitamin K, their origins, their differential characteristics of absorption and metabolism, their relative effects on gammacarboxylation of various proteins implicated in hemostasis andcoagulation, in bone calcification are not well known even by experts in these fields. These misunderstandings explain errors in recommendations for public and for patients. This review will not expose again the fundamentals on vitamins K as presented in the paper by Marc Guillaumont published in 2000 in this same journal. This 2011 review will try to update our actual knowledge and most of all will insist on their practical implications especially on the management of oral anticoagulant treatments since until recently vitamin K antagonist was the only available type of such a treatment. Several examples illustrate the need for a better understanding of this subject. The fear that diet vitamin K could deregulate the equilibrium of oral vitamin K antagonist treatment leads to recommend a quite total suppression of vitamin K containing components in the diet of anticoagulated patients. This leads to an opposite effect: a high sensitivity to vitamin K and to disequilibrium of the anticoagulant treatment while a comprehensivemoderate and regular diet intake of vitamin K first facilitates the food choice of the patients but also helps to stabilise the treatment of chronically anticoagulated patients. Vitamin K plays a role in bone calcification and in osteoporosis prevention. Until recently the food supplementation with vitamin K in view of preventing osteoporosis in general population was strongly limited due to fear to affect the treatment equilibrium in anticoagulated patients. While an understanding that the effects of moderate supplementation in vitamin K has no or limited effect on anticoagulation and on the long run could at the opposite help to stabilize the daily level of anticoagulation in patients chronically treated with vitamin K.

This review article gives a survey of the generally accepted biosynthetic pathways that lead to fat-soluble vitamins (vitamin A, vitamin D, vitamin E, vitamin K, the corresponding provitamins, and the closely related ubiquinones and plastoquinones) in animals, plants, and microorganisms. Extensively used are reaction schemes, sequences, and mechanisms with the enzymes involved, with detailed explanations using chemical principles and mechanisms.

Background and aims A high dietary intake of vitamin K1 (phylloquinone) and vitamin K2 (menaquinones) is thought to decrease cardiovascular disease risk by reducing vascular calcification. The objective of this study is to explore if there is a relationship between phylloquinone and menaquinones intake and risk of PAD. Methods We investigated the association between intake of phylloquinone and menaquinones with PAD in a prospective cohort with 36,629 participants. Occurrence of PAD was obtained by linkage to national registries. Baseline intake of phylloquinone and menaquinones was estimated using a validated food-frequency questionnaire. Multivariate Cox regression was used to estimate adjusted hazard ratio's for the association. Results During 12.1 years (standard deviation 2.1 years) of follow-up, 489 incident cases of PAD were documented. Menaquinones intake was associated with a reduced risk of PAD with a hazard ratio (HR) of 0.71, 95% CI; 0.53–0.95 for the highest versus lowest quartile. A stronger association was observed ( p interaction 0.0001) in participants with hypertension (HR Q4 versus Q1 0.59; 95% CI 0.39–0.87) or diabetes (HR Q4 versus Q1 0.56; 95% CI 0.18–1.91), though confidence intervals were wide in the small (n = 530) diabetes stratum. Phylloquinone intake was not associated with PAD risk. Conclusions High intake of menaquinones was associated with a reduced risk of PAD, at least in hypertensive participants. High intake of phylloquinone was not associated with a reduced risk of PAD. [ABSTRACT FROM AUTHOR]

We describe a method for the determination of the two major urinary metabolites of vitamin K as the methyl esters of their aglycone structures, 2-methyl-3-(3′-3′-carboxymethylpropyl)-1,4-naphthoquinone (5C-aglycone) and 2-methyl-3-(5′-carboxy-3′-methyl-2′-pentenyl)-1,4-naphthoquinone (7C-aglycone), by HPLC with electrochemical detection (ECD) in the redox mode. Urinary salts were removed by reversed-phase (C18) solid-phase extraction (SPE), and the predominantly conjugated vitamin K metabolites were hydrolyzed with methanolic HCl. The resulting carboxylic acid aglycones were quantitatively methylated with diazomethane and fractionated by normal-phase (silica) SPE. Final analysis was by reversed-phase (C18) HPLC with a methanol-aqueous mobile phase. Metabolites were detected by amperometric, oxidative ECD of their quinol forms, which were generated by postcolumn coulometric reduction at an upstream electrode. The assay gave excellent linearity (typically, r2 ⩾ 0.999) and high sensitivity with an on-column detection limit of

Objetives: Nowadays it is recognised that vitamin K plays an important role in bone health. It is necessary for the gamma-carboxylation of osteocalcin (the most important non-collagen protein in the bone), making the osteocalcin function. There are two important forms of vitamin K (vitamin K1 and vitamin K2), which come from different sources and have different biological activity. Epidemiological studies suggest that a diet with high levels of vitamin K is associated with a lower risk of hip fractures in older men and in women. However, controlled randomised clinical trials, carried out with supplements of vitamin K1 or K2 in the white population do not show an increase in bone mineral density (BMD) in most of the different areas of the skeleton. Supplementation with vitamin K1 and K2 may reduce the risk of fracture, but the clinical trials which include fractures as a final result have methodological limitations, so clinical trials with greater numbers of patients, and which are better designed, would be needed in order to prove the efficacy of vitamin K1 and K2 in relation to fractures. In conclusion, we may say that there is currently insufficient evidence to recommend the routine use of vitamin K for the prevention of osteoporosis and fractures in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objetives: Nowadays it is recognised that vitamin K plays an important role in bone health. It is necessary for the gamma-carboxylation of osteocalcin (the most important non-collagen protein in the bone), making the osteocalcin function. There are two important forms of vitamin K (vitamin K1 and vitamin K2), which come from different sources and have different biological activity. Epidemiological studies suggest that a diet with high levels of vitamin K is associated with a lower risk of hip fractures in older men and in women. However, controlled randomised clinical trials, carried out with supplements of vitamin K1 or K2 in the white population do not show an increase in bone mineral density (BMD) in most of the different areas of the skeleton. Supplementation with vitamin K1 and K2 may reduce the risk of fracture, but the clinical trials which include fractures as a final result have methodological limitations, so clinical trials with greater numbers of patients, and which are better designed, would be needed in order to prove the efficacy of vitamin K1 and K2 in relation to fractures. In conclusion, we may say that there is currently insufficient evidence to recommend the routine use of vitamin K for the prevention of osteoporosis and fractures in postmenopausal women. [ABSTRACT FROM AUTHOR]

Abstract Following a request from the European Commission, pursuant to Article 13 of Regulation (EC) No 1924/2006, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a health claim related to vitamin K2 and contribution to the normal function of the heart and blood vessels. The food constituent that is the subject of the claim, vitamin K2, is sufficiently characterised. The claimed effect, contribution to the normal function of the heart and blood vessels, is a beneficial physiological effect. The proposed target population is the general population. In weighing the evidence, the Panel took into account the absence of human intervention studies from which conclusions could be drawn for the scientific substantiation of the claim, the inconsistency of the results reported in two cross‐sectional studies regarding arterial calcification in women, that the results of two prospective cohort studies are in conflict regarding the risk of coronary heart disease associated with vitamin K2 intakes, that high intakes of vitamin K2 were associated with a significantly lower degree of aortic calcification in one prospective cohort study after adjustment for confounders, and that the evidence provided for a proposed mechanism is weak. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the dietary intake of vitamin K2 and contribution to the normal function of the heart and blood vessels.

Recent reports have attributed the potential health benefits of vitamin K beyond its function to activate hepatic coagulation factors. Moreover, several studies have suggested that menaquinones, also known as vitamin K2, may be more effective in activating extra-hepatic vitamin K-dependent proteins than phylloquinone, also known as vitamin K1. Nevertheless, present dietary reference values (DRV) for vitamin K are exclusively based on phylloquinone, and its function in coagulation. The present review describes the current knowledge on menaquinones based on the following criteria for setting DRV: optimal dietary intake; nutrient amount required to prevent deficiency, maintain optimal body stores and/or prevent chronic disease; factors influencing requirements such as absorption, metabolism, age and sex. Dietary intake of menaquinones accounts for up to 25 % of total vitamin K intake and contributes to the biological functions of vitamin K. However, menaquinones are different from phylloquinone with respect to their chemical structure and pharmacokinetics, which affects bioavailability, metabolism and perhaps impact on health outcomes. There are significant gaps in the current knowledge on menaquinones based on the criteria for setting DRV. Therefore, we conclude that further investigations are needed to establish how differences among the vitamin K forms may influence tissue specificities and their role in human health. However, there is merit for considering both menaquinones and phylloquinone when developing future recommendations for vitamin K intake. [ABSTRACT FROM PUBLISHER]

Abstract: Vitamin K has been purported to play an important role in bone health. It is required for the gamma-carboxylation of osteocalcin (the most abundant noncollagenous protein in bone), making osteocalcin functional. There are 2 main forms (vitamin K1 and vitamin K2), and they come from different sources and have different biological activities. Epidemiologic studies suggest a diet high in vitamin K is associated with a lower risk of hip fractures in aging men and women. However, randomized controlled trials of vitamin K1 or K2 supplementation in white populations did not increase bone mineral density at major skeletal sites. Supplementation with vitamin K1 and K2 may reduce the risk of fractures, but the trials that examined fractures as an outcome have methodological limitations. Large well-designed trials are needed to compare the efficacies of vitamin K1 and K2 on fractures. We conclude that currently there is not enough evidence to recommend the routine use of vitamin K supplements for the prevention of osteoporosis and fractures in postmenopausal women. [Copyright &y& Elsevier]

Vitamin K is present in the diet in the forms of phylloquinone and menaquinones. Phylloquinone, which is the major dietary source, is concentrated in leafy plants and is the vitamin K form best characterized in terms of food composition and dietary intakes. In contrast, menaquinones are the product of bacterial production or conversion from dietary phylloquinone. Food composition databases are limited for menaquinones and their presence in foods varies by region. Dietary intakes of all forms of vitamin K vary widely among age groups and population subgroups. Similarly, the utilization of vitamin K from different forms and food sources appear to vary, although our understanding of vitamin K is still rudimentary in light of new developments regarding the menaquinones. [ABSTRACT FROM AUTHOR]

It has recently been proposed that in addition to Nomenclature, Classification and Identification, Comprehending Microbial Diversity may be considered as the fourth tenet of microbial systematics [Staley JT () The Bulletin of BISMiS, 1(1): 1-5]. As this fourth goal implies a fundamental understanding of microbial speciation, this perspective article argues that translation of bacterial genome sequences into metabolic features may contribute to the development of modern polyphasic taxonomic approaches. Genome-scale metabolic network reconstructions (GSMRs), which are the result of computationally predicted and experimentally confirmed stoichiometric matrices incorporating all enzyme and metabolite components encoded by a genome sequence, provide a platform that can illustrate bacterial speciation. As the topology and the composition of GSMRs are expected to be the result of adaptive evolution, the features of these networks may provide the prokaryotic taxonomist with novel tools for reaching the fourth tenet of microbial systematics. Through selected examples from the Actinobacteria, which have been inferred from GSMRs and experimentally confirmed after phenotypic characterisation, it will be shown that this level of information can be incorporated into modern polyphasic taxonomic approaches. In conclusion, three specific examples are illustrated to show how GSMRs will revolutionize prokaryotic systematics, as has previously occurred in many other fields of microbiology. [ABSTRACT FROM AUTHOR]

Vitamin K is traditionally recognized for its role in blood clotting. More recently, new roles for vitamin K have emerged. The current evidence for the role of vitamin K in bone, cardiovascular, and reproductive health will be discussed. There will be a particular focus on populations who could be at risk for vitamin K deficiency. [ABSTRACT FROM PUBLISHER]

Vitamin K acts as a cofactor during the γ-carboxylation of vitamin K-dependent proteins. Undercarboxylated osteocalcin (ucOC) is a suggested biomarker of vitamin K status. The +2255 polymorphism of the vitamin K epoxide reductase gene (VKORC1) was shown to be associated with the recycling rate of the active form of vitamin K. We investigated the association between dietary vitamin K intake and serum ucOC and hypothesized that this association might vary by VKORC1 genotype. ucOC and total intact osteocalcin (iOC) concentrations were quantified using specific ELISA tests in serum samples of 548 male and female participants (aged 18–81 years) of the Bavarian Food Consumption Survey II. ucOC was expressed relative to iOC (ucOC/iOC ratio). Dietary intake of vitamin K (phylloquinone and menaquinones) was estimated from three 24 h dietary recalls using previously published food composition data. The association between dietary vitamin K intake and ucOC/iOC ratio was analysed using linear and non-linear regression models. Median intakes of phylloquinone/menaquinones were 83·4/37·6 μg/d in men and 79·6/29·8 μg/d in women, respectively. As expected, vitamin K intake was significantly inversely associated with the ucOC/iOC ratio. The ucOC/iOC ratio differed significantly across variants of the +2255 polymorphism in the VKORC1 gene. Stratification by VKORC1+2255 genotype revealed that only in carriers of the GG genotype (39 % of all participants) did the ucOC/iOC ratio significantly decrease with increasing intake of vitamin K. Thus, the results show that the inverse association between dietary vitamin K intake and serum ucOC depends on a functionally relevant allelic variant of the VKORC1 gene. [ABSTRACT FROM PUBLISHER]

Summary: Vitamin K deficiency bleeding (VKDB) is a rare and potentially life-threatening bleeding disorder of early infancy. Vitamin K stores are low at birth; thereafter breast-fed infants are at risk because of low concentrations in human milk. Classical VKDB occurs in the first week of life, is related to delayed or inadequate feeding and is readily prevented by small doses of vitamin K at birth. Late VKDB peaks at 3–8weeks, typically presents with intracranial haemorrhage often due to undiagnosed cholestasis with resultant malabsorption of vitamin K. Diagnosis can be difficult but PIVKA-II measurements can provide confirmation even several days post-treatment. Without vitamin K prophylaxis, the incidence of late VKDB in Europe is 4–7 cases per 105 births; it is higher in SE Asia where in rural, low-income areas some 0.1% of affected infants may suffer intracranial bleeding. Late VKDB is largely preventable with parenteral vitamin K providing the best protection. The efficacy of oral prophylaxis is related to the dose and frequency of administration. Most multi-dose oral regimens provide protection for all except a small reservoir of infants with undetected hepatobiliary disease. Targeted surveillance of high-risk groups (e.g. biliary atresia) offers a novel approach to assess efficacy of prophylaxis. [Copyright &y& Elsevier]

Cell-free supernatant from Shewanella oneidensis MR-1 reduced carbon tetrachloride to chloroform, a suspension of Fe(III) and solid Fe(III) to iron (II). The putative reducing agent was tentatively identified as menaquinone-1 (MQ-1)—a water-soluble menaquinone with a single isoprenoid residue in the side chain. Synthetic MQ-1 reduced carbon tetrachloride to chloroform and amorphous iron (III) hydroxide to iron (II). To test the generality of this result among menaquinones, the reductive activities of vitamin K2 (MQ-7)—a lipid-associated menaquinone with 7 or 8 isoprenoid residues—was evaluated. This molecule also reduced carbon tetrachloride to chloroform and iron (III) to iron (II). The results indicate that molecules within the menaquinone family may contribute to both the extracellular and cell-associated reduction of carbon tetrachloride and iron (III). [ABSTRACT FROM AUTHOR]