Phylloquinone Intake Research Articles

Vitamin K status, cardiovascular disease, and all-cause mortality: a participant-level meta-analysis of 3 US cohorts

Vitamin K-dependent proteins in vascular tissue affect vascular stiffness and calcification, which is associated with cardiovascular disease (CVD) and all-cause mortality. To determine the association of circulating vitamin K concentrations with CVD and all-cause mortality by conducting a participant-level meta-analysis. We obtained individual participant-level data from the Health, Aging, and Body Composition Study, the Multi-Ethnic Study of Atherosclerosis, and the Framingham Offspring Study, known cohorts with available measures of fasting circulating phylloquinone (vitamin K-1) and confirmed CVD events and mortality. Circulating phylloquinone was measured in a central laboratory from fasting blood samples and categorized as ≤0.5 nmol/L, >0.5-1.0 nmol/L, and >1.0 nmol/L. Multivariable Cox proportional hazard regression with multiple imputations was used to evaluate the association of circulating phylloquinone with incident CVD and all-cause mortality risk. Among 3891 participants (mean age 65±11 y; 55% women; 35% nonwhite), there were 858 incident CVD events and 1209 deaths over a median of 13.0 y. The risk of CVD did not significantly differ according to circulating phylloquinone [fully adjusted HR (95% CI) relative to >1.0 nmol/L: ≤0.5 nmol/L, 1.12 (0.94, 1.33); >0.5-1.0 nmol/L, 1.02 (0.86, 1.20)]. Participants with ≤0.5 nmol/L circulating phylloquinone had an adjusted 19% higher risk of all-cause mortality compared with those with >1.0 nmol/L [fully adjusted HR (95% CI): 1.19 (1.03, 1.38)]. Mortality risk was similar in participants with >0.5-1.0 nmol/L compared with >1.0 nmol/L [fully adjusted HR (95% CI): 1.04 (0.92, 1.17)]. Low circulating phylloquinone concentrations were associated with an increased risk of all-cause mortality, but not of CVD. Additional studies are needed to clarify the mechanism underlying this association and evaluate the impact of increased phylloquinone intake on cardiovascular and other health outcomes in individuals with low vitamin K status.

Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort

ObjectiveThe role of vitamin K in the regulation of vascular calcification is established. However, the association of dietary vitamins K1 and K2 with risk of coronary heart disease (CHD) is...

Vitamin K-biofortification of eggs: effect on egg quality and hen performance parameters

AbstractVitamin K has important physiological functions which relate to blood coagulation (its classical role), bone health, inhibition of arterial calcification, as well as anti-inflammatory effects. National nutrition survey data have shown that over half of all adults in Ireland and the UK have low vitamin K1 intakes (£1 μg/kg body weight/d). Vitamin K biofortification of food may be an important complementary food-based approach for improving vitamin K intakes. Our study aimed to explore the feasibility of producing vitamin K-biofortified eggs via increasing the vitamin K3 content of the hen diet, and to examine any effects on hen performance and egg/eggshell quality parameters. A 12-week hen feeding trial was conducted in the Agri-Food and Biosciences Institute, Belfast, UK. Hyline chickens (n = 128) were randomized into 4 treatment (T) groups (n = 32 hens/group) and fed diets containing 3 (T1-industry standard), 12.9 (T2), 23.7 (T3) and 45.7 (T4) mg vitamin K3/kg of feed. Hens were provided feed ad libitum and feed intake was recorded weekly. Eggs were collected daily and weighed. While egg quality and vitamin K content was assessed at week 0, 4, 6, 8 and 12, the trial endpoint (week 12) data was prioritized for the current analysis. Total vitamin K content (i.e., vitamin K1 plus menaquinone (MK)-4 and MK-7) of composite samples (n = 12 eggs/treatment), measured using a novel, sensitive liquid chromatography-mass spectrometry method at Teagasc, increased from 22.4 μg/100 g (whole egg) in T1 (control and commercial level of vitamin K3) to 57.8 μg/100 g in T4. MK-4 was the most abundant form of vitamin K found in the eggs. Eggshell weight and eggshell thickness in T2 and T3 (but not T4) were significantly higher than in T1 (by 20–28%, P < 0.05). Likewise, based on colourimetric assessment, yellowness (parameter b*) of the egg yolk in all three biofortified groups was significantly higher compared to T1 (by 27–45%, P < 0.05). Haugh unit of the eggs and hen performance parameters, such as feed intake, feed conversion ratio and egg production, were unaffected by vitamin K-biofortification. In conclusion, increasing the level of addition of vitamin K3 to hen feed significantly increased the total vitamin K content of eggs, and without any evidence of negative effects on egg quality or hen performance. Consumption of an average sized (60 g) vitamin K-biofortified egg could contribute an additional 35 μg total vitamin K. The effects on eggshell parameters could be of importance in terms of revenue loss due to breakages.

Concentrations of Circulating Phylloquinone,but Not Cerebral Menaquinone-4, Are Positively Correlated with a Wide Range of Cognitive Measures: Exploratory Findings in Centenarians

Vitamin K (VK) exists in the form of phylloquinone (PK) and menaquinones (MKs). Roles of VK on cognitive health in the elderly are emerging, but there is limited evidence on VK uptake and metabolism in human brain. The primary objective of this study was to characterize VK distribution in brains of an elderly population with varied cognitive function. In addition, associations among circulating (a biomarker of VK intake) and cerebral VK concentrations and cognition were investigated. Serum or plasma (n=27) and brain samples from the frontal cortex (FC; n=46) and the temporal cortex (TC; n=33) were acquired from 48 decedents (aged 98-107 y; 25 demented and 23 nondemented) enrolled in the Georgia Centenarian Study. Both circulating and brain VK concentrations were measured using HPLC with fluorescence detection. Cognitive assessment was performed within 1 y prior to mortality. Partial correlations between serum/plasma or cerebral VK concentrations and cognitive function were performed, adjusting for covariates and separating by dementia and antithrombotic use. MK-4 was the predominant vitamer in both FC (mean±SD=4.92±2.31 pmol/g, ≥89.15%±5.09% of total VK) and TC (4.60±2.11 pmol/g, ≥89.71%±4.43% of total VK) regardless of cognitive status. Antithrombotic users had 34.0% and 53.9% lower MK-4 concentrations in FC (P<0.05) and TC (P<0.001), respectively. Circulating PK was not correlated with cerebral MK-4 or total VK concentrations. Circulating PK concentrations were significantly associated with a wide range of cognitive measures in nondemented centenarians (P<0.05). In contrast, cerebral MK-4 concentrations were not associated with cognitive performance, either before or after exclusion of antithrombotic users. Circulating VK concentrations are not related to cerebral MK-4 concentrations in centenarians. Cerebral MK-4 concentrations are tightly regulated over a range of VK intakes and cognitive function. Circulating PK may reflect intake of VK-rich foods containing other dietary components beneficial to cognitive health. Further investigation of VK uptake and metabolism in the brain is warranted.

Increasing Dietary Vitamin K Intake Stabilizes Anticoagulation Therapy in Warfarin-Treated Patients with a History of Instability: A 24-week Randomized Controlled Trial (OR36-04-19)

ObjectivesWarfarin (W) is a highly prescribed anticoagulant for the treatment and prevention of thromboembolic diseases. However, anticoagulation stability is often a challenge due to the narrow therapeutic range of the drug. In recent years, dietary vitamin K (VK) has emerged as an important modulator of long-term anticoagulation stability. In trials, patients receiving small doses of supplemental VK (100–150 mg/d) spend significantly more time in the therapeutic range (%TTR) and present fewer bleeding and thrombotic complications. Whether similar beneficial effects can be achieved through diet remains unknown. We determined whether increasing dietary VK intake by ≥150 μg/day improves anticoagulation stability of W-treated patients with a history of INR instability. MethodsWe conducted a 24-week randomized controlled trial at the Anticoagulation Clinics of the Montreal Heart Institute and the Jewish General Hospital (Montreal). The main inclusion criteria were: 1) be anticoagulated for >6 months with a target international normalized ratio (INR) range of 2.0–3.0 or 2.5–3.5, and 2) present a %TTR <50% in the previous 6 months. Patients randomized to the intervention group (VK) received dietary counsel to increase their VK intake by ≥150 μd/day through specific food choices, recipes and cooking strategies. Patients from the control (C) group received general dietary information of similar intensity. Warfarin therapy was monitored weekly by INR. The primary clinical outcome was anticoagulation stability as defined by %TTR > 70% during weeks 4 through 24. Groups were compared in an intention-to-treat method using the exact Fisher test. ResultsIn total, 49 patients aged 32–85 years completed the study. Mean (±SEM) %TTR over the assessment period were 67.7 ± 3.4 and 61.4 ± 3.5 for the VK and C groups, respectively (ns). Increasing dietary VK intakes resulted in a greater proportion of patients with %TTR > 70% over the assessment period. Specifically, 14 of the 28 patients (50%) from the VK group met the criteria versus 4 of the 21 patients (19%) from the C group (P = 0.026). ConclusionsIncreasing VK intake ≥150 μd/day through diet strategies improves anticoagulation stability of W-treated patients with a history of anticoagulation instability. Funding SourcesThis study was funded by the CIHR.

Epigenome-wide Association Study of Plasma Phylloquinone Response to Phylloquinone Supplementation (OR31-04-19)

ObjectivesGenetics explains a small amount of the variability in the response of plasma phylloquinone to phylloquinone intake. Whether epigenetic modifications, which reflect interactions between the genome and environment, are related to the plasma phylloquinone response to supplementation has not been examined. The objective of this study was to conduct an epigenome-wide association study (EWAS) to identify genetic loci whose methylation levels associate with changes in circulating phylloquinone in response to phylloquinone supplementation. MethodsWe used data from a 3-year, randomized controlled, phylloquinone supplementation (500 ug/d) trial in healthy older adults. One hundred four white participants in the supplementation group who passed filters for adherence to the protocol (mean age = 68(5.0) years, 56% female) were classified as responders or non-responders according to their change in plasma phylloquinone. Of these, 24 participants with the smallest (non-responders) and 24 participants with the largest (responders) change in plasma phylloquinone were selected for DNA methylation analysis. DNA was isolated from baseline blood samples. Bisulfite-converted DNA for these 48 individuals was analyzed using the Illumina MethylationEPIC microarray platform at the Yale Center for Genome Analysis in New Haven, CT. The association of responder status with methylation beta-value at each site was examined using logistic regression adjusted for control-probe principal components. ResultsForty (38%) of the 104 participants had changes in plasma phylloquinone that classified them as non-responders. A single CpG site (cg10918016 in NCOR2) was associated with plasma phylloquinone responder status at genome-wide Bonferroni level of significance (P < 6.4 × 10−8). In the presence of moderate genomic inflation (λ = 1.21), 5239 sites showed suggestive associations (Benjamini-Hochberg FDR < 0.2). ConclusionsDNA methylation levels may contribute toward the inter-individual plasma phylloquinone response to supplementation. Larger studies in diverse populations are warranted to clarify the causal influence of methylation on the vitamin K status. Funding SourcesStudy supported by the USDA Agricultural Research Service under Cooperative Agreement No. 58-1950-7-707, NHLBI T32HL069772, and the Gerald Cassidy Student Research Award.*JMK and KW contributed equally to this research. Supporting Tables, Images and/or Graphs▪

Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study

Multiple observational studies and small-scale intervention studies suggest that high vitamin K intake is associated with improved markers for cardiovascular health. Circulating phylloquinone solely represents phylloquinone (vitamin K1) intake, while dephosphorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) represents both phylloquinone and menaquinone (vitamin K2) intake. This study aims to investigate the causal relationship between genetically predicted vitamin K concentrations and the risk of CHD via a two-sample Mendelian Randomization approach. We used data from three studies: the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study, CARDIOGRAMplusC4D and the UK Biobank, resulting in 103,097 CHD cases. Genetically predicted vitamin K concentrations were measured using SNPs related to circulating phylloquinone and dp-ucMGP. We calculated a genetic risk score (GRS) including four SNPs (rs2108622, rs2192574, rs4645543 and rs6862071) related to circulating phylloquinone levels from a genome wide association study. Rs4236 was used as an instrumental variable for dp-ucMGP. Inverse-variance weighted (IVW) analysis was used to obtain Risk Ratios (RRs) for the causal relationship between phylloquinone and dp-ucMGP concentrations and CHD risk. Using the genetic score for circulating phylloquinone, we found that circulating phylloquinone was not causally related to CHD risk (RR 1.00 (95%-CI: 0.98; 1.04)). Lower genetically predicted dp-ucMGP concentration was associated with a lower CHD risk with a RR of 0.96 (95%-CI: 0.93; 0.99) for every 10μg/L decrease in dp-ucMGP. This study did not confirm a causal relationship between circulating phylloquinone and lower CHD risk. However, lower dp-ucMGP levels may be causally related with a decreased CHD risk. This inconsistent result may reflect the influence of menaquinones in the association with CHD.

Assessment of Dietary Intake of Vitamin K and Maximum Limits for Vitamin K in Food Supplements

Assessment of Dietary Intake of Vitamin K and Maximum Limits for Vitamin K in Food Supplements

Vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial

Vitamin K inhibits prostate cancer cells, and an altered expression of vitamin K-dependent proteins in prostate tumors has been linked to their aggressiveness and progression. However, little is known about the effect of vitamin K intake on prostate cancer in human populations. We evaluated the associations of dietary intake of phylloquinone (vitamin K-1), menaquinones (vitamin K-2), and total vitamin K with the development of prostate cancer among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. Dietary intake of vitamin K was assessed with the Dietary Questionnaire (DQX) at baseline and the Dietary History Questionnaire (DHQ) at the third anniversary of randomization by using high-performance liquid chromatography-based food-composition data obtained from the USDA and published studies. During a median follow-up of 11.8 y, 2978 cases of prostate cancer (including 490 advanced cases) were identified from the 28,356 men who completed DQX. Similarly, 2973 cases of prostate cancer (including 647 advanced cases) were documented from the 48,090 men who completed DHQ. Cox proportional hazards regression was used to estimate prostate cancer risk in relation to the dietary intake of vitamin K. After adjustment for confounders, dietary intakes of phylloquinone, menaquinones, and total vitamin K, assessed with either the DQX or DHQ, were not significantly associated with the risk of advanced, nonadvanced, and total prostate cancer. These results remained virtually the same when vitamin K intake was modeled as a categorical (divided into quintiles) or continuous (per IQR increase) variable or after outliers of total vitamin K intake (defined as a value that falls above the sum of third quartile and twice the IQR) were excluded. The present study does not suggest that vitamin K intake influences the occurrence of total and advanced prostate cancer in the general US population.

Plasma Response to Deuterium-Labeled Vitamin K Intake Varies by TG Response, but Not Age or Vitamin K Status, in Older and Younger Adults

Phylloquinone is the primary form of vitamin K in the diet and circulation. Large intra- and interindividual variances in circulating phylloquinone have been partially attributed to age. However, little is known about the nondietary factors that influence phylloquinone absorption and metabolism. Similarly, it is not known if phylloquinone absorption is altered by the individual's existing vitamin K status. The purpose of this secondary substudy was to compare plasma response with deuterium-labeled phylloquinone intake in older and younger adults after dietary phylloquinone depletion and repletion. Forty-two older [mean±SD age: 67.2±8.0 y; body mass index (BMI; in kg/m2): 25.4±4.6; n=12 men, 9 women] and younger (mean±SEM age: 31.8±6.6 y; BMI: 25.5±3.3; n=9 men, 12 women) adults were maintained on sequential 28-d phylloquinone depletion (∼10 µg phylloquinone/d) and 28-d phylloquinone repletion (∼500 µg phylloquinone/d) diets. On the 23rd d of each diet phase, participants consumed deuterated phylloquinone-rich collard greens (2H-phylloquinone). Plasma and urinary outcome measures over 72 h were compared by age group, sex, and dietary phase via 2-factor repeated-measures ANOVA. The plasma 2H-phylloquinone area under the curve (AUC) did not differ in response to phylloquinone depletion or repletion, but was 34% higher in older than in younger adults (P=0.02). However, plasma 2H-phylloquinone AUC was highly correlated with the serum triglyceride (TG) AUC (r2=0.45). After adjustment for serum TG response, the age effect on the plasma 2H-phylloquinone AUC was no longer significant. Plasma 2H-phylloquinone response did not differ between phylloquinone depletion and repletion in older and younger adults. The age effect observed was explained by the serum TG response and was completely attenuated after adjustment. Plasma response to phylloquinone intake, therefore, seems to be a predominantly lipid-driven effect and not dependent on existing vitamin K status. More research is required to differentiate the effect of endogenous compared with exogenous lipids on phylloquinone absorption. This trial was registered at clinicaltrials.gov as NCT00336232.

Nutritional effect on age-related cataract formation and progression.

To provide a comprehensive summary of the latest evidence-based data on nutrients linked to the pathogenesis of cataract formation and progression. This summary of peer-reviewed publications emphasizes the ongoing effort to modulate the cataractogenous process through nutrition, and points at an only weak evidence for the contribution of a specific nutrient to this process. Although observational studies successfully demonstrated a positive correlation between specific nutrients intake and age-related cataract, such evidence was usually lacking in following interventional studies. Three metanalyses point towards a beneficial effect of high intake of vitamin C, vitamin E and vitamin A on the risk of age-related cataract. New studies point at a protective effect of a high intake of vitamin K1 and vitamin D but negate the influence of Mediterranean diet or an overall high dairy consumption on the progression of cataract in a subgroup of patients. Sterols are candidate nutrients for future investigation. Nutrition rich in fruits and vegetables, and a high dietary intake of vitamins A, C, D, E and K1 may be inversely associated with the risk of age-related cataract. More studies involving patients in a wide range of nutritional status are required to establish the long-term benefit of nutritional supplements.

Abstract P272: Dietary Intake of Vitamin K and the Risk of Incident Pulmonary Embolism in the Nurses’ Health Study

Introduction: Vitamin K, which is consumed as phylloquinone (K 1 ) and menaquinone (K 2 ), impacts some vitamin-K dependent proteins involved in hemostasis. It is unknown whether dietary intake of phylloquinone and menaquinone are associated with incident pulmonary embolism (PE) risk. Hypotheses: Dietary intake of phylloquinone and menaquinone will be positively associated with the risk of incident PE and, in secondary analyses, idiopathic PE. Methods: Eligible women were Nurses’ Health Study participants free of venous thromboembolism (VTE) at 1984 baseline (n=74,821). Participants completed a food frequency questionnaire every four years (1984-2010) and we calculated intake of phylloquinone and menaquinone. Eligible PE cases were confirmed via medical record review or participant reconfirmation, or self-reported among persons with prior cancer. Cases were defined as idiopathic in the absence of cancer, recent surgery, and trauma. Cox Proportional Hazards models estimated hazard ratios and 95% confidence intervals for PE associated with time-varying energy-adjusted quintiles of phylloquinone, and separately, menaquinone. Two models adjusted for time-varying covariates, first including lifestyle and medical factors and next adding energy-adjusted nutrients. Secondary analyses estimated idiopathic PE risk. Results: We identified 568 incident PE events during 1,328,669 person-years. In analyses adjusted for lifestyle and medical factors, there was no evidence of a linear association between incident PE risk and energy-adjusted quintiles of phylloquinone intake (linear p-trend across quintile medians = 0.37) or menaquinone intake (linear p-trend = 0.57). Results for idiopathic PE risk were similarly null, as were results after further adjustment for nutrients (Table). Conclusions: In this study of U.S. women, there was no evidence of a linear association between energy-adjusted quintiles of phylloquinone or menaquinone intake and incident PE risk, before or after adjustment for other nutrients.

Vitamin K2 in multiple sclerosis patients.

SummaryBackgroundVitamin 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).MethodsWe 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.ResultsOverall, 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (10.1007/s00508-018-1328-x) contains supplementary material, which is available to authorized users.

Phylloquinone Intake Is Associated with Cardiac Structure and Function in Adolescents

Associations between childhood vitamin K consumption and cardiac structure and function have not been investigated. We determined associations between phylloquinone (vitamin K-1) intake and left ventricular (LV) structure and function in adolescents. We assessed diet with three to seven 24-h recalls and physical activity (PA) by accelerometry in 766 adolescents (aged 14-18 y, 50% female, 49% black). Fat-free soft tissue (FFST) mass and fat mass were measured by dual-energy X-ray absorptiometry. LV structure [LV mass (g)/height (m)2.7 (LV mass index) and relative wall thickness] and function [midwall fractional shortening (MFS) and ejection fraction] were assessed by echocardiography. Associations were evaluated by comparing the LV structure and function variables across tertiles of phylloquinone intake. Prevalence and OR of LV hypertrophy (LV mass index >95th percentile for age and sex) were also assessed by phylloquinone tertiles. The prevalence of LV hypertrophy progressively decreased across tertiles of phylloquinone intake (P-trend < 0.01). Multinomial logistic regression-adjusting for age, sex, race, Tanner stage, systolic blood pressure, FFST mass, fat mass, socioeconomic status, PA, and intakes of energy, fiber, calcium, vitamin C, vitamin D, and sodium-revealed that compared with the highest phylloquinone intake tertile (reference group), the adjusted OR for LV hypertrophy was 3.3 (95% CI: 1.2, 7.4) for those in the lowest phylloquinone intake tertile. When LV structure variables were compared across phylloquinone intake tertiles adjusting for the same covariates, there were significant linear downward trends for LV mass index (6.5% difference, tertile 1 compared with tertile 3) and relative wall thickness (9.2% difference, tertile 1 compared with tertile 3; both P-trend ≤ 0.02). Conversely, significant linear upward trends across phylloquinone intake tertiles were observed for MFS (3.4% difference, tertile 1 compared with tertile 3) and ejection fraction (2.6% difference, tertile 1 compared with tertile 3; both P-trend < 0.04). Our adolescent data suggest that subclinical cardiac structure and function variables are most favorable at higher phylloquinone intakes.

Reproducibility and relative validity of a food frequency questionnaire to estimate intake of dietary phylloquinone and menaquinones.

This study aims to investigate the reproducibility and relative validity of the Dutch food frequency questionnaire (FFQ), to estimate intake of dietary phylloquinone and menaquinones compared with 24-h dietary recalls (24HDRs) and plasma markers of vitamin K status. In a cross-sectional study among 63 men and 58 women, the FFQ was completed three times over a 1-year period and the reproducibility was calculated over these measurements. Twelve-monthly 24HDR were collected to estimate relative validity. In addition, the relative validity of the FFQ, compared with plasma phylloquinone and desphospho-uncarboxylated matrix Gla protein (dpucMGP), was assessed cross-sectionally among 507 postmenopausal women. Intraclass correlations showed a good reproducibility, with correlations ranging from 0.65 to 0.83. The relative validity for phylloquinone intake compared with 24HDR was lower for women (rs=0.28) than men (rs=0.40). The relative validity, compared with 24HDR, for intake of short-chain menaquinones were ranging between 0.30 and 0.34. Long-chain menaquinones showed good relative validity (rs=0.60-0.69). Plasma phylloquinone concentrations were weakly correlated with phylloquinone intake (rs=0.16 (0.07-0.24). Plasma dpucMGP was negatively but weakly correlated with phylloquinone intake (rs=-0.09 (-0.18; -0.01)) and long-chain menaquinones (rs=-0.13 (-0.21; -0.04)), but not with short-chain menaquinones (rs=-0.04 (-0.13; 0.05)). The FFQ is reproducible to rank subjects for phylloquinone and menaquinone intake.The relative validity of our FFQ, compared with 24HDR, to estimate intake of phylloquinone and short-chain menaquinones was low, but the relative validity for long-chain menaquinones was good. The relative validity of our FFQ, compared with plasma phylloquinone and dpucMGP, was relatively low for both phylloquinone and menaquinone intake.

Vegetables and Mixed Dishes Are Top Contributors to Phylloquinone Intake in US Adults: Data from the 2011-2012 NHANES

Background: Phylloquinone is the most abundant form of vitamin K in US diets. Green vegetables are considered the predominant dietary source of phylloquinone. As our food supply diversifies and expands, the food groups that contribute to phylloquinone intake are also changing, which may change absolute intakes. Thus, it is important to identify the contributors to dietary vitamin K estimates to guide recommendations on intakes and food sources.Objective: The purpose of this study was to estimate 1) the amount of phylloquinone consumed in the diet of US adults, 2) to estimate the contribution of different food groups to phylloquinone intake in individuals with a high or low vegetable intake (≥2 or <2 cups vegetables/d), and 3) to characterize the contribution of different mixed dishes to phylloquinone intake.Methods: Usual phylloquinone intake was determined from NHANES 2011-2012 (≥20 y old; 2092 men and 2214 women) and the National Cancer Institute Method by utilizing a complex, stratified, multistage probability-cluster sampling design.Results: On average, 43.0% of men and 62.5% of women met the adequate intake (120 and 90 μg/d, respectively) for phylloquinone, with the lowest self-reported intakes noted among men, especially in the older age groups (51-70 and ≥71 y). Vegetables were the highest contributor to phylloquinone intake, contributing 60.0% in the high-vegetable-intake group and 36.1% in the low-vegetable-intake group. Mixed dishes were the second-highest contributor to phylloquinone intake, contributing 16.0% in the high-vegetable-intake group and 28.0% in the low-vegetable-intake group.Conclusion: Self-reported phylloquinone intakes from updated food composition data applied to NHANES 2011-2012 reveal that fewer men than women are meeting the current adequate intake. Application of current food composition data confirms that vegetables continue to be the primary dietary source of phylloquinone in the US diet. However, mixed dishes and convenience foods have emerged as previously unrecognized but important contributors to phylloquinone intake in the United States, which challenges the assumption that phylloquinone intake is a marker of a healthy diet. These findings emphasize the need for the expansion of food composition databases that consider how mixed dishes are compiled and defined.

Abstract 5312: No association between vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)

Abstract Prostate cancer is one of the most common cancers worldwide. The etiology of prostate cancer largely remains unclear, with almost all established risk factors (e.g. age, race, family history) being not modifiable. Ecological, migrant, and temporal trend studies suggest that diet plays role in the occurrence of prostate cancer, but few nutrients that alter its risk have been identified from case-control and cohort studies. Vitamin K has two forms that naturally occur in foods, i.e., phylloquinone (vitamin K1) and menaquinone (vitamin K2). While phylloquinone is abundant in green leafy vegetables and some vegetable oils, menaquinone is primarily derived from fermented food products (e.g. cheese). Although experimental studies have shown that vitamin K inhibits the growth of various cancer cell lines (including prostate cancer cells), only one epidemiologic study has investigated the association between vitamin K intake and prostate cancer risk. In that German study, a significant inverse association with advanced prostate cancer was observed for menaquinone intake. The present study thus sought to investigate the associations between intake of vitamin K (from both dietary and supplemental sources) and the risk of total and advanced prostate cancer among 28,356 PLCO participants. A total of 2978 cases of prostate cancer (including 490 advanced cases) have been documented during a median follow up of 11.8 years. Advanced prostate cancer were defined as disease in stage II with a Gleason score of 8-10, stage III, or stage IV. Usual dietary intake among study subjects was assessed with Dietary Questionnaire (DQX) at baseline and Dietary History questionnaire (DHQ) at year 3, both of which were developed and validated by the National Cancer Institute. Dietary intake of phylloquinone and menaquinones were calculated using the USDA National Nutrient Database for Standard Reference (Release 23), supplemented with menaquinone data from published studies. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for dietary intake of phylloquinone and menaquinones in relation to prostate cancer risk. After adjustment for confounders, no statistically significant associations were found between vitamin K intake estimated from the DQX and prostate cancer risk [HR (95% CI) for the highest quintile vs. the lowest quintile: 0.99 (0.87, 1.13) for total vitamin K, 0.99 (0.87, 1.12) for phylloquinone, and 1.02 (0.87, 1.18) for total menaquinones]. Overall null results were also observed when additional analysis was carried out by the stage of the disease (i.e. advanced and non-advanced cases) and for vitamin K intake data assessed with the DHQ. In summary, the present study revealed that intake of total vitamin K and its two natural forms was not associated with the risk of total and advanced prostate cancer. Citation Format: Maggie Hoyt, Michael Reger, Jianjun Zhang. No association between vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5312. doi:10.1158/1538-7445.AM2017-5312

Non-Traditional Aspects of Renal Diets: Focus on Fiber, Alkali and Vitamin K1 Intake.

Renal diets for advanced chronic kidney disease (CKD) are structured to achieve a lower protein, phosphate and sodium intake, while supplying adequate energy. The aim of this nutritional intervention is to prevent or correct signs, symptoms and complications of renal insufficiency, delaying the start of dialysis and preserving nutritional status. This paper focuses on three additional aspects of renal diets that can play an important role in the management of CKD patients: the vitamin K1 and fiber content, and the alkalizing potential. We examined the energy and nutrients composition of four types of renal diets according to their protein content: normal diet (ND, 0.8 g protein/kg body weight (bw)), low protein diet (LPD, 0.6 g protein/kg bw), vegan diet (VD, 0.7 g protein/kg bw), very low protein diet (VLPD, 0.3 g protein/kg bw). Fiber content is much higher in the VD and in the VLPD than in the ND or LPD. Vitamin K1 content seems to follow the same trend, but vitamin K2 content, which could not be investigated, might have a different pattern. The net endogenous acid production (NEAP) value decreases from the ND and LPD to the vegetarian diets, namely VD and VLPD; the same finding occurred for the potential renal acid load (PRAL). In conclusion, renal diets may provide additional benefits, and this is the case of vegetarian diets. Namely, VD and VLPD also provide high amounts of fibers and Vitamin K1, with a very low acid load. These features may have favorable effects on Vitamin K1 status, intestinal microbiota and acid-base balance. Hence, we can speculate as to the potential beneficial effects on vascular calcification and bone disease, on protein metabolism, on colonic environment and circulating levels of microbial-derived uremic toxins. In the case of vegetarian diets, attention must be paid to serum potassium levels.

Vitamin K intake and the risk of fractures: A meta-analysis.

The association between dietary vitamin K intake and the risk of fractures is controversial. Therefore we perform a meta-analysis of cohort or nested case–control studies to investigate the relationship between dietary vitamin K intake and the risk of fractures. A comprehensive search of PubMed and EMBASE (to July 11, 2016) was performed to identify cohort or nested case–control studies providing quantitative estimates between dietary vitamin K intake and the risk of fractures. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were pooled by using a random-effects model. Four cohort studies and one nested case–control study, with a total of 1114 fractures cases and 80,982 participants, were included in our meta-analysis. Vitamin K intake in all included studies refers exclusively to the intake of phylloquinone (vitamin K1), which is the predominant form of vitamin K in foods. We observed a statistically significant inverse association between dietary vitamin K intake and risk of fractures (highest vs. the lowest intake, RR = 0.78, 95% CI: 0.56–0.99; I2 = 59.2%, P for heterogeneity = .04). Dose–response analysis indicated that the pooled RR of fracture for an increase of 50 μg dietary vitamin K intake per day was 0.97 (95% CI: 0.95–0.99) without heterogeneity among studies (I2 = 25.9%, P for heterogeneity = .25). When stratified by follow-up duration, the RR of fracture for dietary vitamin K intake was 0.76 (95% CI: 0.58–0.93) in studies with more than 10 years of follow-up. Our study suggests that higher dietary vitamin K intake may moderately decrease the risk of fractures.

Phylloquinone Intakes and Food Sources and Vitamin K Status in a Nationally Representative Sample of Irish Adults

Background: Data from a nationally representative sample of 18- to 64-y-old Irish adults conducted in 1999 highlighted low phylloquinone intakes. That survey, however, did not include older adults (aged ≥65 y), a subgroup that is potentially at higher risk of low phylloquinone intakes, or a biomarker of vitamin K status.Objectives: The objectives of this work were to measure the phylloquinone intake and its adequacy and the serum percentage of undercarboxylated osteocalcin (%ucOC), a vitamin K status biomarker, in a nationally representative sample of Irish adults aged 18–90 y, and to compare these newer data on dietary phylloquinone in adults aged 18–64 y with those from the previous survey.Methods: Data and biobanked serum samples from the National Adult Nutrition Survey, a randomly selected sample of Irish adults aged 18–90 y (N = 1500), were accessed. Phylloquinone intakes were estimated from 4-d food diary data and were compared across age groups (18–35, 36–50, 51–64, and ≥65 y). Serum %ucOC was assessed by immunoassay (n = 692).Results: The mean ± SD intake of phylloquinone from all sources was 85.2 ± 59.1 μg/d, 99% of which was derived from food. Phylloquinone intakes and serum %ucOC were significantly (P < 0.05) lower (14–25%) and higher (27–39%), respectively, in the 18- to 35-y age group than in the 36- to 50-y, 51- to 64-y, and ≥65-y age groups (no differences between these 3 groups; P > 0.2 in all cases). Mean phylloquinone intakes had increased (P < 0.01) modestly (6 μg/d) in 18–64-y-olds across a decade. Of the total study population, 55% had phylloquinone intakes below the United Kingdom recommended intake of 1 μg ⋅ kg body weight–1 ⋅ d–1.Conclusion: Our study shows that younger adults (aged 18–35 y) appear to be at higher risk of inadequate vitamin K intake and lower vitamin K status, the health implications of which are unclear and warrant further investigation.