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Objective: To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a community-based sample of men and women. Subjects/Methods: A cross-sectional study of 1762 participants of the Framingham Offspring Study (919 women; mean age 59 years). Vitamin K status was measured as plasma phylloquinone and serum percent undercarboxylated osteocalcin (ucOC), and vitamin D was measured using plasma 25-hydroxyvitamin D (25(OH)D). Associations between vitamin K status and vitamin D status with biologically plausible nongenetic factors were assessed using stepwise regression. Heritability and linkage were determined using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Results: Nongenetic factors accounted for 20.1 and 12.3% of the variability in plasma phylloquinone in men and women respectively, with triglycerides and phylloquinone intake being the primary correlates. In men 12.2% and in women 14.6% of the variability in %ucOC was explained by nongenetic factors in our models. Heritability estimates for these vitamin K status biomarkers were nonsignificant. Season, vitamin D intake, high-density lipoprotein (HDL) cholesterol and waist circumference explained 24.7% (men) and 24.2% (women) of the variability in plasma 25(OH)D. Of the three vitamins examined, only 25(OH)D was significantly heritable (heritability estimate=28.8%, P <0.01), but linkage analysis of 25(OH)D did not achieve genome-wide significance. Conclusions: Variability in biomarkers of vitamin K status was attributed to nongenetic factors, whereas plasma 25(OH)D was found to be significantly heritable. Further studies are warranted to investigate genetic loci influencing vitamin D status.

Data on the association between vitamin D status and actual change in glycemic measures are limited. We examined the prospective association between a predicted 25-hydroxyvitamin D (25(OH)D) score and change in fasting plasma glucose concentration over a mean follow-up of 7 years, in 2571 men and women (mean age 54 years) without diabetes in the Framingham Offspring Study cohort. After adjustment for age, sex, body mass index and fasting plasma glucose at baseline, higher predicted 25(OH)D score at baseline was associated with a smaller 7-year increase in fasting plasma glucose concentrations (0.23 mmol/l versus 0.35 mmol/l for highest versus lowest tertile of 25(OH)D score, respectively, P -trend=0.002). Vitamin D status may be an important determinant for change in fasting plasma glucose concentration among middle-aged and older adults without diabetes.

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. 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 (r.sub.s=0.28) than men (r.sub.s=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 (r.sub.s=0.60-0.69). Plasma phylloquinone concentrations were weakly correlated with phylloquinone intake (r.sub.s=0.16 (0.07-0.24). Plasma dpucMGP was negatively but weakly correlated with phylloquinone intake (r.sub.s=-0.09 (-0.18; -0.01)) and long-chain menaquinones (r.sub.s=-0.13 (-0.21; -0.04)), but not with short-chain menaquinones (r.sub.s=-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.

Background/Objectives: 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. Subjects/Methods: 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. Results: 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 (r s =0.28) than men (r s =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 (r s =0.60–0.69). Plasma phylloquinone concentrations were weakly correlated with phylloquinone intake (r s =0.16 (0.07-0.24). Plasma dpucMGP was negatively but weakly correlated with phylloquinone intake (r s =−0.09 (−0.18; −0.01)) and long-chain menaquinones (r s =−0.13 (−0.21; −0.04)), but not with short-chain menaquinones (r s =−0.04 (−0.13; 0.05)). Conclusions: 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.

The brain is enriched with sphingolipids, which are important membrane constituents and major lipid signaling molecules that have a role in motor and cognitive behavior. Vitamin K has been implicated in brain sphingolipid metabolism for more than 30 years. The in vitro and in vivo studies to date suggest a role of vitamin K in the regulation of multiple enzymes involved in sphingolipid metabolism within the myelin-rich regions in the brain. However, the precise mechanisms of action are not well understood. Further, the physiological consequences of the observed effects of vitamin K on sphingolipid metabolism have not been systematically studied.

Objective: To examine the feasibility of using phylloquinone intake as a marker for coronary heart disease (CHD) and stroke risk in women. Design and setting: Nurses' Health Study, a prospective cohort study during 1984-2000. Dietary data were collected in 1984, 1986, 1990, and 1994 using a validated semiquantitative food frequency questionnaire. Subjects: A total of 72 874 female nurses, aged 38-65 y, without previously diagnosed angina, myocardial infarction (MI), stroke, or cancer at baseline. Main outcome measures: Incidence of nonfatal MI, CHD deaths, total CHD events, ischemic, and total strokes. Results: There were 1679 CHD events (1201 nonfatal) and 1009 strokes (567 ischemic). After adjustment for age and lifestyle factors associated with cardiovascular disease risk, the multivariate relative risks (RR) (95% CI) of total CHD from the lowest to the highest quintile category of phylloquinone intake were 1 (reference), 0.80 (0.69-0.94), 0.86 (0.74-1.00), 0.77 (0.66-0.99), and 0.79 (0.68-0.92), P for trend=0.01. Further adjustment for dietary intakes of saturated fat, polyunsaturated fat, trans fatty acids, eicosapentaenoic, and docosahexaenoic acids, cereal fiber, and folate attenuated the association (RR comparing extreme quintiles 0.84 [0.71-1.00], P for trend=0.12). Incidence rates of total or ischemic strokes were not associated with phylloquinone intake. Conclusion: The data suggest that high phylloquinone intake may be a marker for low CHD risk. Dietary and lifestyle patterns associated with phylloquinone intakes, rather than intake of the nutrient itself, might account for all or part of the weak association.

Dietary Guidelines have emerged over the past 30 years recommending that Americans limit their consumption of total fat and saturated fat as one way to reduce the risk of a range of chronic diseases. However, a low-fat diet is not a no-fat diet. Dietary fat clearly serves a number of essential functions. For example, maternal energy deficiency, possible exacerbated by very low-fat intakes (< 15% of energy), is one key determinant in the etiology of low birth weight. The debate continues over recommendations for limiting total fat and saturated fatty acid intake in children. Recent evidence indicates that diets with adequate energy providing less than 30% of energy from fat are sufficient to promote normal growth and normal sexual maturation. More attention needs to be devoted to the effect of dietary fat reduction on the nutrient density of children's diets. The association between dietary fat and CHD has been extensively studied. Diets high in saturated fatty acids and trans fatty acids increase LDL cholesterol levels, and in turn, the risk of heart disease. The relationship between high-carbohydrate/low-fat diets and CHD is more ambiguous because high-carbohydrate diets induce dyslipidemia in certain individuals. Obesity among adults and children is now of epidemic proportions in the United States. High-fat diets leading to excessive energy intakes are strongly linked to the increasing obesity in the United States. However, the prevalence of obesity has increased during the same time period that dietary fat intake (both in absolute terms and as a percentage of total dietary energy) has decreased. These trends suggest that a concomitant decrease in total dietary energy and modifications of other lifestyle factors, such as physical activity, also need to be emphasized. Obesity is also an independent risk factor for the development of diabetes. The current availability of fat-modified foods offers the potential for dietary fat reduction and treatment of the comorbidities associated with diabetes. However, to date, few studies have documented the effectiveness of fat-modified foods as part of a weight loss regimen or in reduction in CHD risks among individuals with diabetes mellitus. The association between total dietary fat and cancer is still under debate. While there is some evidence demonstrating associations between dietary fat intake and cancers of the breast, prostate, and colon, there are serious methodologic issues, including the difficulty in differentiating the effects of dietary fat independent of total energy intake. Reported total fat and saturated fatty acid intakes as a percentage of total energy have been declining over the past 30 years in the United States. Despite this encouraging trend, the majority of individuals--regardless of age--do not report consuming a diet that meets the levels of fat and saturated fatty acids recommended by the Dietary Guidelines for Americans. On a relative basis, saturated fat intake has gone down less than has total fat intake. Individuals of all ages who report consuming a diet with < or = 30% of energy from fat consistently have lower energy intakes. Given the increasing rates of obesity in the United States at an earlier and earlier age, dietary fat reduction may be an effective part of an overall strategy to balance energy consumption with energy needs. In each of the age/gender groups reporting consumption of < or = 30% of energy from fat and less than 10% of energy from saturated fatty acids, fat-modified foods play a more important role in their diets than for people who are consuming higher levels of fat and saturated fat. The data are clear than fat-modified foods make a more significant contribution to diets of consumers with low-fat intakes. While one cannot argue cause and effect from the results presented, the patterns of fat-modified foods/low-fat intakes are consistent. The focus on overall diet quality is often lost in the national obsession with lowering fat inta

Warfarin has been successfully used in the medical management of thromboembolic disease for nearly six decades. It is widely assumed that a dietary vitamin K-warfarin interaction exists. To avoid this potential interference with the efficacy of warfarin in stable anticoagulation, patients typically receive instructions to consume a constant dietary intake of vitamin K. While dark, green vegetables are primary sources of dietary vitamin K, these foods are not commonly consumed on a daily basis in the United States. However, there still exists dietary resistance to warfarin that is attributable to vitamin K. Based on food analysis studies on vitamin K, it is now known that dietary vitamin K is found in certain plant oils and prepared foods containing these plant oils, such as baked goods, margarines, and salad dressings. The preparation of foods with vitamin K-rich oils may also contribute to a diet-warfarin interaction, although this has yet to be confirmed in a clinical trial. A dose-response of vitamin K on the effect of warfarin anti-coagulation has not yet been established. However, there are sufficient data to suggest that a constant dietary intake of vitamin K that meets current dietary recommendations of 65-80 microgram/day is the most acceptable practice for patients on wafarin therapy. Vitamin K composition data for commonly consumed foods are now available and may facilitate successful anticoagulation for patients being treated with warfarin.

Osteocalcin and matrix Gla protein (MGP) are two vitamin K-dependent proteins present in bone and cartilage. Transgenic mice models were recently developed to isolate the function of each of these proteins. While osteocalcin-deficient mice have increased bone formation, MGP-deficient mice have abnormal calcification leading to osteopenia, fractures, and premature death owing to arterial calcification

An experimental study of the normalized three-jet rate of b quark events with respect to light quarks events (light=ℓ≡u,d,s) has been performed using the CAMBRIDGE and DURHAM jet algorithms. The data used were collected by the DELPHI experiment at LEP on the Z peak from 1994 to 2000. The results are found to agree with theoretical predictions treating mass corrections at next-to-leading order. Measurements of the b quark mass have also been performed for both the b pole mass: Mb and the b running mass: mb(MZ). Data are found to be better described when using the running mass. The measurement yields: \\(m_b(M_Z)=2.850.18 (stat) 0.13 (exp) 0.19 (had) 0.12 (theo) GeV/c^2.\\)for the CAMBRIDGE algorithm.This result is the most precise measurement of the b mass derived from a high energy process. When compared to other b mass determinations by experiments at lower energy scales, this value agrees with the prediction of quantum chromodynamics for the energy evolution of the running mass. The mass measurement is equivalent to a test of the flavour independence of the strong coupling constant with an accuracy of 7 ‰.