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The health-promoting properties of vitamin K stimulate the growing interest in this compound, which translates into the development of new analytical methodologies for its determination. New, more efficient methods of its isolation are sought, paying increasingly more attention to the methods within currently available extraction techniques that, owing to the optimization of the process, not only increase the extraction efficiency but are also economical and environmentally friendly. This article proposes a procedure for the extraction and analysis of one of the vitamin K vitamers, i.e., vitamin K1, using PLE and LC-MS/MS. It has been shown that the PLE technique can be optimized with a mathematical model—accelerating and reducing the costs of the extraction process—which, together with process automation, bodes well for industrial applications. The optimized process was used to extract vitamin K1 from various vegetables, showing very different contents of the test compound ranging from 1.22 to 114.30 µg/g dry weight for avocado and spinach, respectively. In addition, by showing the effect of water within the material subjected to extraction on the variable yield of vitamin K1, attention was drawn to the need to standardize the analytical methods used in assessing the quality of food products. [ABSTRACT FROM AUTHOR]

Vitamin K (VK) is an essential micronutrient impacting many systems in the body. This lipid-soluble vitamin is found in various plant and animal products and is absorbed via the lymphatic system. This biomolecule’s importance to human health includes but is not limited to its promotion of brain, cardiovascular, bone, and immune functions. These biological properties are also necessary for maintaining domesticated animal health. The synergistic impact of both VK and vitamin D (VD) maximizes these health benefits, specifically for the circulatory and skeletal systems. This manuscript reviews VK’s properties, molecular structures, nutrikinetics, mechanisms of action, daily requirements, safety in supplemental form, biomarkers used for its detection, and impacts on various organs. The purpose of synthesizing this information is to evaluate the potential uses of VK for the treatment or prevention of diseases.

Vitamin K, as a natural protector of our blood, bones, kidneys, and brain, is essential for human health. It is also considered an effective anti-aging agent with comprehensive biological effects, including antifungal, antibacterial, anti-inflammatory, analgesic, and even antioxidant properties. Of these, the least is known about the antioxidant properties of natural vitamin K. To fill this gap, this study compared the antioxidant properties of extracts obtained from commonly consumed green plants with different vitamin K contents with the activity of vitamin K standard solutions at concentrations corresponding to the vitamin K contents in the extracts. Various measurement methods were used in the research (i.e., DPPH, FRAP, CUPRAC, and the β-carotene bleaching test). Among the tested methods, the β-carotene bleaching test is the most sensitive in the assessment of this unusual compound. In light of the data presented, the antioxidant response of vitamin K alone is dose-dependent. However, in extracts, the activity of this compound is modulated by other constituents present in them. As a result, the activity does not always correlate with vitamin K content. The presented data supplement the knowledge about the antioxidant properties with the contribution resulting from the presence of vitamin K in green plant extracts. [ABSTRACT FROM AUTHOR]

In this study, we developed a column-switching high-performance liquid chromatography (HPLC) method with fluorescence detection for the analysis of vitamin K. Column-switching is accomplished by changing the direction of flow using a switching valve with a set time program. Using this method, three vitamin K, phylloquinone (PK), menaquinone-4 (MK-4), and menaquinone-7 (MK-7), were separated and identified with high sensitivity, and impurities were eliminated. This method was used to determine the vitamin K content in meat, fish meat, snails, bivalves, sea urchins, seaweeds, vegetables, tea, soy products, milk products, and supplements. The results showed that chicken showed the highest content of MK-4 (15.35 ± 0.35 μg/100 g), matcha showed the highest content of PK (3069.66±80.10 μg/100 g), and dried natto showed the highest content of MK-7 (3997.57±79.42 μg/100 g). This method can also be used to analyze vitamin K in supplements and pharmaceuticals. The results of this study revealed that different manufacturers add different types of vitamin K to their commercial supplements and infant formulas. The developed method provides highly reproducible and quantitative results and allows for the rapid analysis of the three vitamin K types. Thus, the method developed in this study may aid the sequential analysis of vitamin K in different samples to assess food nutrients. [ABSTRACT FROM AUTHOR]

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.

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). 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. 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. • Higher dietary vitamin K1 was inversely associated with mortality. • Specific benefits were observed for cardiovascular disease (CVD) mortality. • A nadir in benefit was observed from vitamin K1 intakes of ∼80 μg/day. • These relationships were independent of lifestyle and CVD-related risk factors. • Vitamin K1-rich foods (green leafy vegetables) should be promoted for CV health. [ABSTRACT FROM AUTHOR]

The health-promoting properties of vitamin K stimulate the growing interest in this compound, which translates into the development of new analytical methodologies for its determination. New, more efficient methods of its isolation are sought, paying increasingly more attention to the methods within currently available extraction techniques that, owing to the optimization of the process, not only increase the extraction efficiency but are also economical and environmentally friendly. This article proposes a procedure for the extraction and analysis of one of the vitamin K vitamers, i.e., vitamin K1, using PLE and LC-MS/MS. It has been shown that the PLE technique can be optimized with a mathematical model—accelerating and reducing the costs of the extraction process—which, together with process automation, bodes well for industrial applications. The optimized process was used to extract vitamin K1 from various vegetables, showing very different contents of the test compound ranging from 1.22 to 114.30 µg/g dry weight for avocado and spinach, respectively. In addition, by showing the effect of water within the material subjected to extraction on the variable yield of vitamin K1, attention was drawn to the need to standardize the analytical methods used in assessing the quality of food products.

Porphyromonas gingivalis is the etiological agent of chronic periodontitis. Menadione (vitamin K 3) and phylloquinone (vitamin K 1) 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. We investigated the effects of menadione and phylloquinone on the growth of two W83 strains and seven ATCC 33277 strains of P. gingivalis. 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. 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. • Both menadione and phylloquinone support the growth of cultured Porphyromonas gingivalis. • Menadione inhibited growth in some strains whereas phylloquinone did not. • The use of phylloquinone is preferable as a growth factor. [ABSTRACT FROM AUTHOR]

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.

Vitamin K, as a natural protector of our blood, bones, kidneys, and brain, is essential for human health. It is also considered an effective anti-aging agent with comprehensive biological effects, including antifungal, antibacterial, anti-inflammatory, analgesic, and even antioxidant properties. Of these, the least is known about the antioxidant properties of natural vitamin K. To fill this gap, this study compared the antioxidant properties of extracts obtained from commonly consumed green plants with different vitamin K contents with the activity of vitamin K standard solutions at concentrations corresponding to the vitamin K contents in the extracts. Various measurement methods were used in the research (i.e., DPPH, FRAP, CUPRAC, and the β-carotene bleaching test). Among the tested methods, the β-carotene bleaching test is the most sensitive in the assessment of this unusual compound. In light of the data presented, the antioxidant response of vitamin K alone is dose-dependent. However, in extracts, the activity of this compound is modulated by other constituents present in them. As a result, the activity does not always correlate with vitamin K content. The presented data supplement the knowledge about the antioxidant properties with the contribution resulting from the presence of vitamin K in green plant extracts.

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Katrine Aagaard Lentz,1 Julie Vahlgren,2 Ditte Hansen,2,3 Mario Plebani,4 Maria Fusaro,4,5 Lars Melholt Rasmussen,6 Jette Jakobsen,7 Jens Jørgen Sloth,7 Henrik Post Hansen,3 Jens Rikardt Andersen1 1Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; 2Department of Nephrology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark; 3Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 4Department of Medicine, University of Padova, Padova, Italy; 5National Research Council, Institute of Clinical Physiology, Pisa, Italy; 6Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; 7National Food Institute, Technical University of Denmark, Lyngby, DenmarkCorrespondence: Ditte Hansen, Email ditte.hansen.04@regionh.dkPurpose: 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.Keywords: hemodialysis, phylloquinone, menaquinone, nutrition

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Quantification of vitamin K1 in serum is still quite a challenge for most analytical laboratories. For long, protein precipitation (PP) coupled with liquid–liquid extraction (LLE) or solid phase extraction (SPE) is the only choice for sample preparation before LC-MS/MS analysis. The objective of this study is to establish a novel method for the simple and rapid quantification of K1. To this end, three issues are illuminated in the first place: (i) the release efficiency of K1 is influenced by the type of precipitator and the volume ratio of serum to precipitator during PP; (ii) the absolute recovery of K1 will be compromised by the partition effect during extraction; (iii) the volume of injected serum per run should be proper rather than high to prevent the potential ion suppression effect. Benefitting from these findings, a single-step PP method is developed for K1 quantification for the first time. For pretreatment, isopropanol (100 μL), instead of the frequently used methanol, ethanol and acetonitrile, is utilized to release K1 from serum (25 μL), which realize the excellent release efficiency (>90%) and dilution effect (1:4) simultaneously. After validation, the method can provide favorable accuracy (91.5–112.2%) and precision (less than13.5%) in the wide concentration range (0.1–2.5 ng/mL). As a result, such method may provide a feasible and high-throughput alternative for evaluating K1 status in practice.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Vitamin K (VK), and particularly phylloquinone (VK1), is an essential micronutrient whose stability in aquafeeds has not been extensively evaluated. Losing stability can lead to nutritional deficiency, which is known to hamper fish development and physiology. Gut microbiota also plays a key role in host health through the interaction with several biological processes. The present study evaluated the best storing conditions of aquafeeds when supplemented in VK1 and intestinal microbiota modulation in Senegalese sole (Solea senegalensis) juveniles. Aquafeeds with a high level of VK1 supplementation required storage at −20 °C for short-term (up to 7 days) and at −80 °C for long-term (up to three months) to ensure optimal preservation. Furthermore, gut bacterial communities of Senegalese sole specimens fed with a commercial feed supplemented with VK1 showed a better-balanced population of microorganisms in the intestine, which might improve Senegalese sole health during the ongrowing phase. These results provide the practical guidelines for the proper storing of aquafeeds in the industry when supplemented with VK1 and highlight the potential benefits of dietary VK1 supplementation for a balanced intestinal microbiota and overall fish health. 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. [ABSTRACT FROM AUTHOR]

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. • Phylloquinone was measured in 95 samples of Australian horticultural commodities. • Kale contained the greatest concentration (565 μg/100 g) of phylloquinone. • Baby spinach contained 255 μg/100 g phylloquinone. • Concentrations in some foods differed to those measured in other countries. • The need for region-specific phylloquinone food composition data is supported. [ABSTRACT FROM AUTHOR]

Vitamin K collectively describes fat‐soluble vitamins containing 2‐methyl‐1,4‐naphthoquinone, including two naturally‐occurring forms: phylloquinone (K1) and a range of menaquinones, MK4‐M13 (K2). Leafy vegetables are the main dietary source of K1, whereas K2 is mainly bacterially synthesised and found in fermented foods, including dairy foods, and some animal sources. Studies suggest that vitamin K may be important for cardiovascular health, due to its role in inhibiting vascular calcification, but food source data, particularly for K2 forms, is lacking. This information could help to clarify recent associations between cheese consumption and reduced CVD risk and would be of use in future epidemiological studies. [ABSTRACT FROM AUTHOR]

Phylloquinone (vitamin K1) and menaquinones (vitamin K2 family) are essential for post-translational γ-carboxylation of a small number of proteins, including clotting factors. These modified proteins have now been implicated in diverse physiological and pathological processes including cancer. Vitamin K intake has been inversely associated with cancer incidence and mortality in observational studies. Newly discovered functions of vitamin K in cancer cells include activation of the steroid and xenobiotic receptor (SXR) and regulation of oxidative stress, apoptosis, and autophagy. We provide an update of vitamin K biology, non-canonical mechanisms of vitamin K actions, the potential functions of vitamin K-dependent proteins in cancer, and observational trials on vitamin K intake and cancer. Phylloquinone (PK) and menaquinones (MKs) are natural compounds essential for the vitamin K cycle of γ-carboxylation, a rare protein post-translational modification. Seventeen γ-carboxylated proteins have been identified that regulate blood coagulation, soft tissue calcification, bone health, and energy metabolism, but the functional impact of γ-carboxylation and the widespread role of these proteins in health and disease have not yet been fully characterized. Overt vitamin K deficiency sufficient to impair blood clotting is rare, but subclinical status is common, especially in elderly populations. Observational studies suggest that low vitamin K intake increases cancer risk, but there are conflicting data on the specific forms of vitamin K that might be beneficial and the types of tumors that might be impacted by vitamin K status. Aggressive tumors exhibit aberrant expression of genes required for vitamin K metabolism and γ-carboxylation. γ-Carboxylated proteins have been identified in tumors and cancer cell lines. [ABSTRACT FROM AUTHOR]

Carboxylative enzymes are involved in many pathways and their regulation plays a crucial role in many of these pathways. In particular, γ‐glutamylcarboxylase (GGCX) converts glutamate residues (Glu) into γ‐carboxyglutamate (Gla) of the vitamin K‐dependent proteins (VKDPs) activating them. VKDPs include at least 17 proteins involved in processes such as blood coagulation, blood vessels calcification, and bone mineralization. VKDPs are activated by the reduced form of vitamin K, naturally occurring as vitamin K1 (phylloquinone) and K2 (menaquinones, MKs). Among these, MK7 is the most efficient in terms of bioavailability and biological effect. Similarly to other trans isomers, it is produced by natural fermentation or chemically in both trans and cis. However, the efficacy of the biological effect of the different isomers and the impact on humans are unknown. Our study assessed carboxylative efficacy of trans and cis MK7 and compared it with other vitamin K isomers, evaluating both the expression of residues of carboxylated Gla‐protein by western blot analysis and using a cell‐free system to determine the GGCX activity by HPLC. Trans MK7H2 showed a higher ability to carboxylate the 70 KDa GLA‐protein, previously inhibited in vitro by warfarin treatment. However, cis MK7 also induced a carboxylation activity albeit of a small extent. The data were confirmed chromatographically, in which a slight carboxylative activity of cis MK7H2 was demonstrated, comparable with both K1H2 and oxidized trans MK7 but less than trans MK7H2. For the first time, a difference of biological activity between cis and trans configuration of menaquinone‐7 has been reported. [ABSTRACT FROM AUTHOR]

Background: Evidence on the association between phylloquinone status and cardiovascular diseases is scarce and conflicting. These inconsistencies may be due to differences in individual characteristics of the study populations, which may modify the association.Objective: This study aimed to evaluate the association between plasma phylloquinone and the risk of first total stroke and its subtypes, and to examine potential effect modifications by body mass index (BMI) in patients with hypertension.Methods: We performed a nested case-control study including 604 first stroke cases and 604 matched controls. The mean age was 62.2 years (range, 45 to 75). Lower BMI was defined as <25 kg/m2, and higher BMI was defined as ≥25 kg/m2. The risks of the first stroke were estimated by odds ratios (ORs) and 95% confidence intervals (CI) using conditional logistic regression. The primary outcome was total stroke or ischemic stroke.Results: The relationship between log-transformed phylloquinone concentration and stroke or ischemic stroke was modified by BMI. Higher phylloquinone levels were associated with lower stroke risk in those with higher BMI. When plasma phylloquinone was assessed as tertiles, the adjusted ORs of first stroke and ischemic stroke for participants with high BMI in tertile 2-3 were 0.70 (95% CI: 0.46,1.08) and 0.57 (95% CI: 0.35,0.92) compared to those in tertile 1, respectively. However, there was no significant association between plasma phylloquinone and risk of first total stroke or ischemic stroke for those with lower BMI. Patients with higher BMI and lower phylloquinone levels had the highest risk of ischemic stroke and showed a statistically significant difference compared to the reference group with lower BMI and higher phylloquinone (OR = 1.80, 95% CI: 1.06, 3.10; P-interaction: 0.017).Conclusions: In Chinese patients with hypertension, there was an inverse association between baseline plasma phylloquinone and risk of first ischemic stroke among those with higher BMI. [ABSTRACT FROM AUTHOR]

Vitamin K is an essential micronutrient required for blood coagulation, regulation of vascular calcification and bone mineralization. Plasma and serum measurements of vitamin K1(phylloquinone, K1) made using high‐performance liquid chromatography with fluorescence detection, or tandem mass spectrometry are used clinically and in population studies to assess vitamin K status. Standard reference materials provide a validation tool for laboratories, helping assure clinical diagnosis and the comparability of data from different populations. We manufactured two K1 standard reference materials, in 2009 (KEQAS SRM‐001) and in 2019 (KEQAS SRM‐002). The target concentrations of K1 were assigned to each SRM using the All Laboratory Trimmed Mean of results reported by selected laboratories enrolled in the Vitamin K External Quality Assurance Scheme (KEQAS). The assigned concentrations of K1 for KEQAS SRM‐001 and SRM‐002 were 0.25 and 0.36 μg/L respectively. In 2019 KEQAS SRM‐001 was re‐analysed simultaneously with KEQAS SRM‐002 to provide traceability between the two standards, therefore aiding comparability of analysis performed using these materials. Both standards were stored as aliquots at −80°C in the dark; annual re‐analysis of the materials indicated that K1 is stable for at least 12 years in these 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]

Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational studies found that low circulating phylloquinone (vitamin K-1) was associated with increased CAC progression, especially in persons treated for hypertension. It is unknown whether hypertension treatment modifies this putative role of vitamin K in clinical CVD risk.Objective: We determined the association between vitamin K status and incident clinical CVD in older adults in the Health ABC (Health, Aging, and Body Composition Study) and whether the association differed by hypertension treatment status.Methods: Plasma phylloquinone was measured in 1061 participants free of CVD (70-79 y of age, 58% women, 39% black). Plasma uncarboxylated MGP [(dp)ucMGP] was measured in a subset of 635 participants. Multivariate Cox models estimated the HR for incident CVD over 12.1 follow-up years. Effect modification by hypertension was tested with the use of interaction terms.Results: Neither low plasma phylloquinone (

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 K 1) and menaquinone-4 (MK-4, vitamin K 2) 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 (NaN 3). 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%. NaN 3 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. • UVA irradiated vitamin K induces typeIand typeIIphototoxic reactions. • The phototoxicity of vitamin K on HaCaT cells was suppressed by NaN 3 and catalase. • The phototoxicity of vitamin K attributed to the generation of singlet oxygen and hydrogen peroxide. • The ROS generated during the photochemical reaction had no impact on the photodegradation of 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]

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

Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia and South America. One of the greatest problems for control of the disease is the emergence of drug resistance, which leads to a need for the development of new antimalarial compounds. The biosynthesis of isoprenoids has been investigated as part of a strategy to identify new targets to obtain new antimalarial drugs. Several isoprenoid quinones, including menaquinone-4 (MK-4/vitamin K2), α- and γ-tocopherol and ubiquinone (UQ) homologs UQ-8 and UQ-9, were previously detected in in vitro cultures of Plasmodium falciparum in asexual stages. Herein, we described for the first time the presence of phylloquinone (PK/vitamin K1) in P. falciparum and discuss the possible origins of this prenylquinone. While our results in metabolic labeling experiments suggest a biosynthesis of PK prenylation via phytyl pyrophosphate (phytyl-PP) with phytol being phosphorylated, on the other hand, exogenous PK attenuated atovaquone effects on parasitic growth and respiration, showing that this metabolite can be transported from extracellular environment and that the mitochondrial electron transport system (ETS) of P. falciparum is capable to interact with PK. Although the natural role and origin of PK remains elusive, this work highlights the PK importance in plasmodial metabolism and future studies will be important to elucidate in seeking new targets for antimalarial drugs. [ABSTRACT FROM AUTHOR]

Background: Vitamin K is a term that comprises a family of structurally related quinones, phylloquinone (PK) and the menaquinones (MKn), that share a common naphthoquinone ring but vary in sidechain length (n) and saturation. Dietary PK is a biosynthetic precursor to tissue menaquinone-4 (MK4), but little is known about the absorption and metabolism of dietary MKn.Objective: To characterize the absorption and metabolism of dietary MKn relative to PK.Methods: In the 4-week diet study, 10-week-old male and female C57BL/6 mice were pair-fed a vitamin K deficient diet (control) or a diet supplemented with 5.0 μmol/kg total PK, MK4, and/or MK9 (separately and in combination). In the 1-week stable isotope study, 12-week-old mice were pair-fed diets containing 2.2 μmol/kg PK (unlabeled control), 2H7PK, 13C11MK4, 2H7MK7, or 2H7MK9. Vitamin K tissue content was quantified by HPLC and/or LC-MS, and concentrations were compared by sex and diet group using 2-factor ANOVA.Results: Regardless of the form(s) of vitamin K provided in the diet, tissue MK4 concentrations did not differ across equimolar supplemented groups in the kidney, adipose, reproductive organ, bone, or pancreas in either males or females in the diet study (all P values > 0.05). Isotopic labeling confirmed the naphthoquinone ring of MK4 in tissues originated from the administered dietary PK or MKn. Despite equimolar supplementation, accumulation of the administered dietary form differed across diet groups in small intestinal segments (all P values < 0.002) and the liver (P < 0.001). Female mice had greater total vitamin K than males in every tissue examined (P < 0.05).Conclusions: Dietary PK, MK4, MK7, and MK9 all served as precursors to tissue MK4 in mice. This study expands our understanding of vitamin K metabolism and supports a common conversion mechanism of all dietary vitamin K forms to MK4. Further investigation of the metabolism and physiological roles of MK4 that may be independent of classical vitamin K function is warranted. [ABSTRACT FROM AUTHOR]

Vitamin K is traditionally connected with blood coagulation, since it is needed for the posttranslational modification of 7 proteins involved in this cascade. However, it is also involved in the maturation of another 11 or 12 proteins that play different roles, encompassing in particular the modulation of the calcification of connective tissues. Since this process is physiologically needed in bones, but is pathological in arteries, a great deal of research has been devoted to finding a possible link between vitamin K and the prevention of osteoporosis and cardiovascular diseases. Unfortunately, the current knowledge does not allow us to make a decisive conclusion about such a link. One possible explanation for this is the diversity of the biological activity of vitamin K, which is not a single compound but a general term covering natural plant and animal forms of vitamin K (K1 and K2) as well as their synthetic congeners (K3 and K4). Vitamin K1 (phylloquinone) is found in several vegetables. Menaquinones (MK4–MK13, a series of compounds known as vitamin K2) are mostly of a bacterial origin and are introduced into the human diet mainly through fermented cheeses. Current knowledge about the kinetics of different forms of vitamin K, their detection, and their toxicity are discussed in this review. [ABSTRACT FROM AUTHOR]

Background Infants have low stores of vitamin K at birth. Dietary intake of phylloquinone (PK) differs dramatically by infant feeding practice, but the contribution of microbially produced vitamin K (menaquinones) to infant vitamin K status is not well understood. Objectives The objective of this study was to investigate determinants of infant fecal vitamin K profiles in mother-infant dyads at 6 wk postpartum. Methods Fecal and breast milk samples were collected from a subsample of breastfeeding (n  = 23) or formula-feeding (n  = 23) mother and infant dyads, delivered vaginally (n  = 26) or by cesarean section (CS) (n  = 20) in the Synergistic Theory and Research on Nutrition and Growth (STRONG) Kids 2 cohort. Vitamin K concentrations in breast milk and feces were analyzed by LC/MS and/or HPLC. Fecal bacterial metagenomes were analyzed to derive taxonomy and vitamin K biosynthetic genes. Multivariate linear modeling was used to assess effects of delivery and feeding modes on infant fecal vitamin K. Results Breast milk contained 1.3 ± 0.2 ng/mL PK, and formula was reported to contain 52 ng/mL PK. Fecal PK was 38-times higher (P < 0.001) in formula-fed than breastfed infants. Infant fecal menaquinones (MKn) MK6, MK7, MK12, and MK13 were higher (P < 0.001) in formula-fed than breastfed infants, whereas MK8 predominated in breastfed and was 5-times higher than formula-fed infants. Total MKn were greater (P < 0.001) in vaginally delivered than CS infants. Relative abundances of 33 bacterial species were affected by feeding mode, 2 by delivery mode, and 4 by both (P < 0.05). Bacterial gene content of 5/12 vitamin K biosynthetic genes were greater (P < 0.05) in breastfed compared with formula-fed infants, and 1 differed by delivery mode. Conclusions Feeding practice and delivery mode influence bacterial vitamin K production in the infant gut. High concentrations of unmetabolized PK in feces of formula-fed infants suggests formula PK content exceeds the absorptive capacity of the infant gut. [ABSTRACT FROM AUTHOR]

Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia and South America. One of the greatest problems for control of the disease is the emergence of drug resistance, which leads to a need for the development of new antimalarial compounds. The biosynthesis of isoprenoids has been investigated as part of a strategy to identify new targets to obtain new antimalarial drugs. Several isoprenoid quinones, including menaquinone-4 (MK-4/vitamin K2), α- and γ-tocopherol and ubiquinone (UQ) homologs UQ-8 and UQ-9, were previously detected in in vitro cultures of Plasmodium falciparum in asexual stages. Herein, we described for the first time the presence of phylloquinone (PK/vitamin K1) in P. falciparum and discuss the possible origins of this prenylquinone. While our results in metabolic labeling experiments suggest a biosynthesis of PK prenylation via phytyl pyrophosphate (phytyl-PP) with phytol being phosphorylated, on the other hand, exogenous PK attenuated atovaquone effects on parasitic growth and respiration, showing that this metabolite can be transported from extracellular environment and that the mitochondrial electron transport system (ETS) of P. falciparum is capable to interact with PK. Although the natural role and origin of PK remains elusive, this work highlights the PK importance in plasmodial metabolism and future studies will be important to elucidate in seeking new targets for antimalarial drugs.

We honor here Hartmut Karl Lichtenthaler, a pioneer of plant physiology, plant biochemistry, plant biophysics, plant molecular biology, and stress physiology. His contributions to the ingenious use of chlorophyll a fluorescence imaging in understanding the physiological processes in leaves stand out. We wish him many happy and productive years of research and educating others.

Background In the last years, evidence that dietary vitamin K could have a role in the cognitive domain has increased. However, data from large trials are limited. The objective of this study was to assess the association of 2 year changes in the dietary intake of vitamin K with cognitive function measured through neuropsychological performance tests. Methods In 5,533 participants of the multicentre PREDIMED-Plus study (48.1% women, age 65.1 ± 4.9 years with overweight/obesity and metabolic syndrome), we assessed the adjusted odds ratios of cognitive function decline according to 2 year changes in vitamin K intake. Participants answered a battery of cognitive function tests and Food Frequency Questionnaires (FFQs) in order to estimate the vitamin K dietary intake. Results After adjusting for potential cofounders, the highest tertile of change of dietary vitamin K intake (median [IQR]; 194.4 μg/d [120.9, 373.1]) was inversely associated with a Mini-Mental State Examination (MMSE) score ≤24 (OR [95% CI]; 0.53 [0.35, 0.79] P for trend = 0.002) compared with a decrease in the intake of vitamin K (median [IQR]; −97.8 μg/d [−292.8, −51.5]). A significant positive association between changes in dietary vitamin K intake and the semantic verbal fluency test scores (OR [95% CI]; 0.69 [0.51, 0.94] P for trend = 0.019) was found. Conclusions An increase of the intake of dietary vitamin K was associated with better cognitive function scores, independently of recognised risk factors for cognitive decline, in an older adult Mediterranean population with high cardiovascular risk. [ABSTRACT FROM AUTHOR]

Objective: Despite operational guidelines, anecdotal evidence suggests that newborn vitamin K1 prophylaxis is not practiced routinely in India. This study determined the coverage of vitamin K1 prophylaxis among newborns in the country.Design: Nationwide cross-sectional data on live births and newborns receiving vitamin K1 during the 2019-2020 reporting period were abstracted from the Health Management Information System (HMIS). The coverage estimates of newborn vitamin K1 prophylaxis were derived nationally and also for individual states and union territories (UT). Additionally, coverage heterogeneities were investigated using classifiers, viz. geography, socio-demographic index (SDI), special developmental categories and institutional birth rate (IBR).Setting: India.Participants: 20 208 804 newborns documented with HMIS.Results: Vitamin K1 was administered to overall 62·36 % newborns (95 % CI: 62·34 to 62·38 %). The Central zone (49·0 %), low SDI states (54·39 %), Empowered Action Group states (53·32 %) and states with low IBR (44·69 %) had the lowest coverage amongst their respective groupings. Across the individual states and UT, the coverage ranged widely from 22·18 % (in Tripura) to 99·38 % (in Puducherry), exhibiting considerable variability (coefficient of variation: 33·74 %) and inequality (Gini coefficient: 0·17). While the coverage in eight states/UT (i.e. Arunachal Pradesh, Manipur, Nagaland, Tripura, Uttar Pradesh, Uttarakhand, Telangana and Andaman & Nicobar Islands) was below 50 %; only five states/UT (i.e. Chandigarh, Gujarat, Goa, Puducherry and Tamil Nadu) achieved above 90 % coverage.Conclusion: Vitamin K1 prophylaxis was not practiced in more than one-third newborns in India. It calls for identifying the barriers, addressing the gaps and implementing newborn vitamin K1 prophylaxis more effectively throughout the country. [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]

Vitamin K is involved many biological processes, such as the regulation of blood coagulation, prevention of vascular calcification, bone metabolism and modulation of cell proliferation. Menaquinones (MK) and phylloquinone vary in biological activity, showing different bioavailability, half-life and transport mechanisms. Vitamin K1 and MK-4 remain present in the plasma for 8–24 h, whereas long-chain menaquinones can be detected up to 96 h after administration. Geometric structure is also an important factor that conditions their properties. cis-Phylloquinone shows nearly no biological activity. An equivalent study for menaquinone is not available. The effective dose to decrease uncarboxylated osteocalcin was six times lower for MK-7 than for MK-4. Similarly, MK-7 affected blood coagulation system at dose three to four times lower than vitamin K1. Both vitamin K1 and MK-7 inhibited the decline in bone mineral density, however benefits for the occurrence of cardiovascular diseases have been observed only for long-chain menaquinones. There are currently no guidelines for the recommended doses and forms of vitamin K in the prevention of osteoporosis, atherosclerosis and other cardiovascular disorders. Due to the presence of isomers with unknown biological properties in some dietary supplements, quality and safety of that products may be questioned. [ABSTRACT FROM AUTHOR]

Evidence suggests there are roles for vitamin K in various chronic disease outcomes, but population-level diet and supplement recommendations are difficult to determine due to high levels of variability in measures of status and response to intake compared to other nutrients. In this preliminary investigation, a blood-based epigenome-wide association study (EWAS) comparing responders and non-responders to phylloquinone (vitamin K1) supplementation (NCT00183001) was undertaken in order to better understand the molecular underpinnings of this observed variability. Responders (n = 24) and non-responders (n = 24) were identified in a prior 3-year phylloquinone supplementation trial based on their changes in plasma phylloquinone concentrations. Differential DNA methylation was identified in multiple regions with previously unknown relationships to phylloquinone absorption and metabolism, such as at the TMEM263 locus. A hypothesis-driven analysis of lipid-related genes highlighted a site in the NPC1L1 gene, supplementing existing evidence for its role in phylloquinone absorption. Furthermore, an EWAS for baseline plasma phylloquinone concentrations revealed a strong correlation between the epigenomic signatures of phylloquinone baseline status and response to supplementation. This work can guide future epigenomic research on vitamin K and contributes to the development of more personalized dietary recommendations for vitamin K.

Nahid Karamzad,1– 3 Esmaeil Faraji,4 Shaghayegh Adeli,2 Kristin Carson‐Chahhoud,5,6 Samaneh Azizi,2 Bahram Pourghassem Gargari2,3 1Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 2Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; 3Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; 4Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 5Australian Centre for Precision Health, School of Health Sciences, University of South Australia, Adelaide, South Australia, Australia; 6School of Medicine, University of Adelaide, Adelaide, South Australia, AustraliaCorrespondence: Bahram Pourghassem GargariDepartment of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, IranEmail bahrampg@yahoo.comBackground: Type 2 diabetes mellitus (T2DM) is a prevalent disorder which accounts for 90– 95% of diabetic patients. The aim of this study was to assess the effects of menaquinone (MK-7) supplementation on glycemic indices, anthropometric indices and lipid profile, among patients with T2DM.Methods: In this double-blind placebo-controlled randomized clinical trial, 60 men and women with T2DM were allocated equally into either the MK-7 (200 μg/day) or the placebo group. Physical activity level and dietary intake were assessed using the international physical activity questionnaire-short form (IPAQ-SF) and a 3-day food record, pre- and post-intervention. Anthropometric measures, blood pressure, glycemic indices and lipid profile including fasting blood sugar (FBS), hemoglobin A1c (HBA1C), fasting insulin (FI), homeostatic model assessment insulin resistance index (HOMA-IR), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were measured at baseline and after twelve weeks.Results: Forty-five patients completed the trial. There were no significant between-group differences for calorie intake, macronutrient intake, physical activity level or anthropometric measures at baseline and at the end of the study. Dietary vitamin K intake increased significantly at the end of the study in the MK-7 (p: 0.02) and placebo (p: 0.001) groups, but intergroup differences were not significant (p: 0.86). FBS (p: 0.01), HbA1c (p: 0.002), fasting insulin (p: 0.01) and HOMA-IR (p: 0.007) decreased significantly in the MK-7 group. Furthermore, after adjustment for the baseline values and changes of vitamin K intake at the end of study, FBS and HbA1C showed significant intergroup changes, and they were significantly lower in the MK-7 group compared to the placebo group. Lipid profile (TG, TC, LDL-C, HDL-C and LDL-C/HDL-C) did not change significantly within or between groups.Conclusion: MK-7 supplementation seems to be effective in the improvement of glycemic indices, but not the lipid profile of patients with T2DM.Clinical Trial Registration: The present study was prospectively registered at the Iranian Registry of Clinical Trials on May 2019 (ID: IRCT20100123003140N22).Keywords: diabetes, dyslipidemia, glycemic status, menaquinone, MK-7, phylloquinone, vitamin K, anthropometric indices

ABSTRACT Objective Recent research has investigated the possible inverse relationship between vitamin K intake and body fat. In addition, an increasing number of studies are supporting a key role for this vitamin in improving lipid profile and insulin sensitivity and reducing the risk of type 2 diabetes mellitus, but little is known about what mechanisms would be involved. Thus, the objective of this study was to investigate the relationship between vitamin K intake (in the form of phylloquinone – PK), body fat, lipid profile and markers of glucose homeostasis in adults and the elderly. Subjects and methods A cross-sectional study with 298 participants (46% men) in the São Paulo Health Survey 2014-2015. Spearman correlations were performed to evaluate the associations between vitamin K intake and the biochemical and body composition measures. Results Among normal-weight male adults (n = 15), PK intake presented a positive correlation with the quantitative insulin sensitivity check index (QUICKI) (r = 0.525; p = 0.045). Among men with high fat mass index (FMI) (n = 101), PK intake had a negative correlation with homeostasis model assessment estimate for β-cell function (HOMA-β) (r = −0.227; p = 0.022). In women with high FMI (n = 122), PK intake had a negative correlation with HOMA-β (r = −0.199, p = 0.032) and insulin (r = −0.207, p = 0.026). No correlations were found between PK intake and lipid profile. Conclusions Our findings support a potential relationship among PK intake, body fat and markers of glucose homeostasis in adults and the elderly.

Vitamin K content of foods is known to vary substantially by geographical location. In Australia, no Vitamin K database of food exists, thereby creating ambiguity when trying to develop national dietary intake guidelines. This investigation aimed to develop a Vitamin K database for commonly consumed foods that are commercially available in Australian supermarkets. The Vitamin K1 (phylloquinone; PK) and K2 (menaquinone; MK4, MK7) content of 60 foods known to contain Vitamin K were assessed (e.g., vegetables fruits, oils, animal products, dairy and fermented foods). A liquid chromatography with tandem mass spectrometry (LCMS/MS) method was developed and used to measure PK and MKs in different foods with an improved chromatographic separation and detection of Vitamin K's and their analogs. The LOD and LOQ for PK and MK4 was 0.1, 0.5 ng/ml and 0.5, 1.0 ng/ml, respectively. The majority foods contained detectable PK (53/60), about half contained MK4 (31/60), and few contained MK7 (3/60). PK was highest in green leafy vegetables, with moderate amounts in oils. Highest MK4 content was in chicken eggs and meat products such as ham and chicken. This database enables nutritional epidemiologist to estimate dietary Vitamin K intake, especially in Australian cohorts, for a range of health outcomes.

Vitamin K (VK) is an essential micronutrient impacting many systems in the body. This lipid-soluble vitamin is found in various plant and animal products and is absorbed via the lymphatic system. This biomolecule's importance to human health includes but is not limited to its promotion of brain, cardiovascular, bone, and immune functions. These biological properties are also necessary for maintaining domesticated animal health. The synergistic impact of both VK and vitamin D (VD) maximizes these health benefits, specifically for the circulatory and skeletal systems. This manuscript reviews VK's properties, molecular structures, nutrikinetics, mechanisms of action, daily requirements, safety in supplemental form, biomarkers used for its detection, and impacts on various organs. The purpose of synthesizing this information is to evaluate the potential uses of VK for the treatment or prevention of diseases.