The association between vitamin K status and knee osteoarthritis features in older adults: the Health, Aging and Body Composition Study.

BACKGROUND: Vitamin K-dependent (VKD) proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence. OBJECTIVE: To clarify what joint tissues vitamin K is relevant to in OA, we investigated the cross-sectional and longitudinal association between vitamin K status and knee OA structural features measured using magnetic resonance imaging (MRI). METHODS: Plasma phylloquinone (PK, vitamin K1) and dephosphorylated-uncarboxylated MGP ((dp)ucMGP) were measured in 791 older community-dwelling adults who had bilateral knee MRIs (mean ± SD age = 74 ± 3 y; 67% female). The adjusted odds ratios (and 95% confidence intervals) [OR (95%CI)] for presence and progression of knee OA features according to vitamin K status were calculated using marginal models with generalized estimating equations (GEEs), adjusted for age, sex, body mass index (BMI), triglycerides and other pertinent confounders. RESULTS: Longitudinally, participants with very low plasma PK (<0.2 nM) were more likely to have articular cartilage and meniscus damage progression after 3 years [OR (95% CIs): 1.7(1.0-3.0), 2.6(1.3-5.2) respectively] compared to sufficient PK (≥ 1.0 nM). Higher plasma (dp)ucMGP (reflective of lower vitamin K status) was associated with higher odds of meniscus damage, osteophytes, bone marrow lesions, and subarticular cysts cross-sectionally [ORs (95% CIs) comparing highest to lowest quartile: 1.6(1.1-2.3); 1.7(1.1-2.5); 1.9(1.3-2.8); 1.5(1.0-2.1), respectively]. CONCLUSION: Community-dwelling men and women with very low plasma PK were more likely to have progression of articular cartilage and meniscus damage. Plasma (dp)ucMGP was associated with presence of knee OA features but not progression. Future studies are needed to clarify mechanisms underlying vitamin Ks role in OA.

Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study.

BACKGROUND: Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults. METHODS: We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts. RESULTS: We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P=0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P=0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P<0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P=0.09). CONCLUSIONS: Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.

Associations of APOE gene polymorphisms with bone mineral density and fracture risk: a meta-analysis.

UNLABELLED: To determine the association of the Apolipoprotein E (APOE) E4 gene polymorphism with bone mineral density (BMD) and fractures we conducted a meta-analysis of 17 reports. Despite lower trochanteric and lumbar BMD in APOE4 carriers, there is insufficient evidence to support a consistent association of APOE with bone health. INTRODUCTION: APOE has been studied for its potential role in osteoporosis risk. It is hypothesized that genetic variation at APOE locus, known as E2, E3, and E4, may modulate BMD through its effects on lipoproteins and vitamin K transport. The purpose of this study was to determine the association of the APOE-E4 gene polymorphism with bone-related phenotypes. METHODS: We conducted a meta-analysis that combined newly analyzed individual data from two community-based cohorts, the Framingham Offspring Study (N = 1,495) and the vitamin K clinical trial (N = 377), with 15 other eligible published reports. Bone phenotypes included BMD measurements of the hip (total hip and trochanteric and femoral neck sites) and lumbar spine (from the L2 to L4 vertebrae) and prevalence or incidence of vertebral, hip, and other fractures. RESULTS: In sex-pooled analyses, APOE4 carriers had a 0.018 g/cm(2) lower weighted mean trochanteric BMD than non carriers (p = 0.0002) with no evidence for between-study heterogeneity. A significant association was also detected with lumbar spine BMD (p = 0.006); however, inter-study heterogeneity was observed. Associations with lumbar spine and trochanteric BMD were observed predominantly in women and became less significant in meta-regression (p = 0.055 and 0.01, respectively). There were no consistent associations of APOE4 genotype with BMD at other skeletal sites or with fracture risk. CONCLUSIONS: Based on these findings, there is insufficient evidence to support a strong and consistent association of the APOE genotype with BMD and fracture incidence.

Vitamin K in hand osteoarthritis: results from a randomised clinical trial.

OBJECTIVES: Vitamin K has bone and cartilage effects, and previously shown to be associated with radiographic osteoarthritis. We evaluated vitamin K's effect on hand osteoarthritis in a randomised controlled trial. METHODS: This was an ancillary study to a randomised controlled trial assessing the effects of phylloquinone supplementation (vitamin K arm) versus placebo on bone loss and vascular calcification among older adults regardless of their vitamin K status. At the final 3-year study visit, we assessed the effects of vitamin K versus placebo on hand x-ray features of osteoarthritis using logistic regression and intention to treat, and also restricted analysis to the subgroup that had insufficient vitamin K concentrations at baseline. RESULTS: This ancillary study had 378 participants (193 in vitamin K arm, 185 in placebo arm). There were no effects of randomisation to vitamin K for radiographic osteoarthritis outcomes. Those with insufficient vitamin K at baseline who attained sufficient concentrations at follow-up had trends towards 47% less joint space narrowing (p = 0.02). CONCLUSIONS: There was no overall effect of vitamin K on radiographic hand osteoarthritis. SUBJECTS: that were insufficient in vitamin K at baseline who attained sufficient concentrations at follow-up may have had a benefit in joint space narrowing. A clinical trial in those who are vitamin K insufficient may be warranted. TRIAL REGISTRATION NUMBER: NCT00183001.

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

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 (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)). 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.

Phylloquinone intake as a marker for coronary heart disease risk but not stroke in women.

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. .

Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables.

BACKGROUND: The putative beneficial effects of an increased consumption of fruit and vegetables have been associated with antioxidant nutrients. However, the effect of fruit and vegetable consumption on the overall antioxidant status in humans is unclear. OBJECTIVE: The objective of this study was to investigate whether a diet rich in fruit and vegetables would affect the antioxidant capacity of human plasma. DESIGN: Thirty-six healthy nonsmokers resided in a metabolic research unit and consumed 2 sets of controlled diets. Diet A contained 10 servings of fruit and vegetables each day for 15 d. Diet B was the same as diet A, except diet B also provided 2 servings of broccoli each day on days 6-10. There was a free-living period of a minimum of 6 wk between the 2 experiments using either diet A or diet B. Fasting plasma antioxidant capacity, measured as oxygen radical absorbance capacity (ORAC), and alpha-tocopherol concentrations were determined on days 1, 6, 11, and 16. RESULTS: The fasting baseline plasma ORAC of these subjects was significantly correlated with their estimated daily intake of total antioxidants from fruit and vegetables during the previous year. Plasma ORAC of these subjects was significantly increased by both diets A and B. This increase in ORAC could not be explained by the increase in the plasma alpha-tocopherol concentration. CONCLUSION: Increased consumption of fruit and vegetables can increase the plasma antioxidant capacity in humans.

Vitamin K intake and hip fractures in women: a prospective study.

BACKGROUND: Vitamin K mediates the gamma-carboxylation of glutamyl residues on several bone proteins, notably osteocalcin. High serum concentrations of undercarboxylated osteocalcin and low serum concentrations of vitamin K are associated with lower bone mineral density and increased risk of hip fracture. However, data are limited on the effects of dietary vitamin K. OBJECTIVE: We investigated the hypothesis that high intakes of vitamin K are associated with a lower risk of hip fracture in women. DESIGN: We conducted a prospective analysis within the Nurses' Health Study cohort. Diet was assessed in 72327 women aged 38-63 y with a food-frequency questionnaire in 1984 (baseline). During the subsequent 10 y of follow-up, 270 hip fractures resulting from low or moderate trauma were reported. RESULTS: Women in quintiles 2-5 of vitamin K intake had a significantly lower age-adjusted relative risk (RR: 0.70; 95% CI: 0.53, 0.93) of hip fracture than women in the lowest quintile (< 109 microg/d). Risk did not decrease between quintiles 2 and 5 and risk estimates were not altered when other risk factors for osteoporosis, including calcium and vitamin D intakes, were added to the models. Risk of hip fracture was also inversely associated with lettuce consumption (RR: 0.55; 95% CI: 0.40, 0.78) for one or more servings per day compared with one or fewer servings per week), the food that contributed the most to dietary vitamin K intakes. CONCLUSIONS: Low intakes of vitamin K may increase the risk of hip fracture in women. The data support the suggestion for a reassessment of the vitamin K requirements that are based on bone health and blood coagulation.

Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects.

The response of osteocalcin and other biochemical markers of vitamin K status to diets formulated to contain different amounts of phylloquinone was assessed in nine healthy subjects aged 20-33 y. Subjects resided in a metabolic ward for two 15-d cycles with a minimum of 6 wk between cycles. A mixed diet containing 100 micrograms phylloquinone/d was fed throughout both cycles; however, the phylloquinone content of one of the cycles was increased to a total of 420 micrograms/d on days 6 through 10 by fortifying corn oil in the diet with phylloquinone (supplemented diet). Total serum osteocalcin concentrations were not affected by either of the dietary treatments. The percentage of undercarboxylated osteocalcin increased an average of 28% over the 15-d cycle with the mixed diet (P < 0.05) and declined significantly an average of 41% with 5 d of the supplemented diet (day 6: 21.9 +/- 1.3%, day 11: 12.8 +/- 1.1%; P = 0.0001) with a rise after the return to the mixed diet (16.7 +/- 1.3%, P < 0.001). Plasma phylloquinone concentrations increased significantly with supplementation (day 6: 0.95 +/- 0.16 nmol/L, day 11: 1.40 +/- 0.29 nmol/L; P < 0.001) and then rapidly returned to presupplementation concentrations on returning to the mixed diet. Twenty-four-hour ratios of urinary gamma-carboxyglutamic acid to creatinine were unchanged with the supplemented diet; however, excretion declined to 91 +/- 2% of baseline after 10 d on the mixed diet (P = 0.01). These results show that undercarboxylated osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid excretion appear to be sensitive measures of vitamin K nutritional status because all of these variables were responsive to changes in dietary intake.

Interaction between vitamin K nutriture and bacterial overgrowth in hypochlorhydria induced by omeprazole.

Subjects taking a hydrogen pump blocking agent (omeprazole) develop bacterial overgrowth of the small intestine. We tested the hypothesis that this bacterial overgrowth produces menaquinones, which would meet the vitamin requirement in situations of vitamin K deficiency. In a crossover-type design, 13 healthy volunteers eating a phylloquinone-restricted diet for 35 d were randomly assigned to take omeprazole during the first period of study or starting on day 15 until the end of the study. Coagulation times, serum osteocalcin [total osteocalcin and undercarboxylated osteocalcin (ucOC)], plasma phylloquinone, urinary gamma-carboxyglutamic acid, and plasma undercarboxylated prothrombin (PIVKA-II) were measured. Plasma phylloquinone concentrations declined 82% with dietary phylloquinone restriction (P < 0.05) and were not significantly different in the period when the diet was combined with omeprazole treatment (P > 0.05). The mean value for PIVKA-II during the phylloquinone-restricted diet significantly increased 5.7-fold from baseline (P < 0.05); however, the combination of omeprazole treatment and the phylloquinone-restricted diet significantly reduced PIVKA-II values by 21% (P < 0.05) compared with the diet period alone. There were no alterations in total or percentage ucOC concentrations during the phylloquinone-restricted diet or during the period of diet plus omeprazole treatment. Our data support the hypothesis that bacterial overgrowth results in the synthesis and absorption of menaquinones. These menaquinones contribute to vitamin K nutriture during dietary phylloquinone restriction, but not enough to restore normal vitamin K status.

Human plasma carotenoid response to the ingestion of controlled diets high in fruits and vegetables.

Plasma carotenoid responses were determined in 36 healthy men and women before and after being fed controlled diets with a moderate amount of fat (26% of total energy) and a high carotenoid content (approximately 16 mg/d) for two 15-d periods. In addition, broccoli (205 g/d) was provided either during the first or the second 15-d residency period in a crossover design. Plasma was digested with lipase and cholesterol esterase, and carotenoids were extracted and measured by using HPLC. Three oxygenated carotenoids (lutein, zeaxanthin, and cryptoxanthin), three hydro-carbon carotenoids (alpha-carotene, all-trans-beta-carotene, and 13-cis-beta-carotene), and four geometric isomers of lycopene (15-cis-, 13-cis-, 9-cis-, and all-trans-lycopene) were separated by using a C30 carotenoid column. A small unidentified peak coeluted with standard 9-cis-beta-carotene and was identified as zeta-carotene (lambda(max) = 400 nm). The concentrations of plasma lutein, cryptoxanthin, alpha-carotene, 13-cis-beta-carotene, all-trans-beta-carotene, and cis- and trans-lycopenes were all significantly increased (P < 0.05) on days 6-16 by the high-fruit and -vegetable diets. The provision of additional broccoli for 5 d to the basic high-carotenoid diet resulted in a further significant increase in the serum concentration of lutein compared with the feeding of the basic high-carotenoid diet alone. Most of the measurable carotenoids of human plasma can be increased by moderate alterations in diet within a short time, although the magnitude of the plasma response may be related to the baseline carotenoid concentrations.

Effects of a hydrogenated form of vitamin K on bone formation and resorption.

BACKGROUND: Hydrogenation of vegetable oils affects blood lipid and lipoprotein concentrations. However, little is known about the effects of hydrogenation on other components, such as vitamin K. Low phylloquinone (vitamin K1) intake is a potential risk factor for bone fracture, although the mechanisms of this are unknown. OBJECTIVE: The objective was to compare the biological effects of phylloquinone and its hydrogenated form, dihydrophylloquinone, on vitamin K status and markers of bone formation and resorption. DESIGN: In a randomized crossover study in a metabolic unit, 15 young adults were fed a phylloquinone-restricted diet (10 microg/d) for 15 d followed by 10 d of repletion (200 microg/d) with either phylloquinone or dihydrophylloquinone. RESULTS: There was an increase and subsequent decrease in measures of bone formation (P = 0.002) and resorption (P = 0.08) after dietary phylloquinone restriction and repletion, respectively. In comparison with phylloquinone, dihydrophylloquinone was less absorbed and had no measurable biological effect on measures of bone formation and resorption. CONCLUSION: Hydrogenation of plant oils appears to decrease the absorption and biological effect of vitamin K in bone.

Response of vitamin K status to different intakes and sources of phylloquinone-rich foods: comparison of younger and older adults.

BACKGROUND: Phylloquinone, found in dark-green vegetables and certain plant oils, is the primary dietary source of the fat-soluble vitamin K. Limited data suggest that the relative bioavailability of phylloquinone from vegetables is lower than that from a supplement. This finding is relevant to the maintenance of optimal vitamin K status. OBJECTIVE: The objective of this study was to compare, in younger and older adults, the relative bioavailability of phylloquinone from a vegetable with that of a fortified oil. DESIGN: In a crossover design with three 15-d residency periods in a metabolic unit, younger and older men and women (n = 36) consumed a mixed diet containing 100 microg phylloquinone/d. During 2 residency periods, the mixed diet was supplemented for 5 d with either broccoli (377 microg phylloquinone/d; broccoli diet) or phylloquinone-fortified oil (417 microg/d; oil diet). The relative bioavailability of phylloquinone was defined by the difference in plasma phylloquinone, percentage serum undercarboxylated osteocalcin (%ucOC), and urinary gamma-carboxyglutamic acid in response to 5 d of supplementation. RESULTS: For both younger and older adults, plasma phylloquinone concentrations were higher (P < 0.001) and %ucOC values were lower (P = 0.001) after the broccoli and oil diets than after the mixed diet only. Overall, the response to broccoli supplementation was not significantly different from the response to the fortified oil in either age group. Urinary gamma-carboxyglutamic acid did not change in response to supplementation. CONCLUSIONS: There was no significant difference in the relative bioavailability of phylloquinone, as evidenced by the lack of a significant difference in plasma phylloquinone and %ucOC between the 2 groups after either the broccoli or oil diets for younger and older adults.

Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women.

BACKGROUND: Vitamin K has been associated with bone mineral density (BMD) and risk of hip fracture. The apolipoprotein (apo) E4 allele (APOE*E4) has been associated with bone fracture through a putative effect on vitamin K transport in blood. OBJECTIVE: The objective was to determine the associations between vitamin K intake, apo E genotype, BMD, and hip fracture in a population-based cohort of elderly men and women. DESIGN: Dietary vitamin K intake was assessed with a food-frequency questionnaire in 335 men and 553 women (average age: 75.2 y) participating in the Framingham Heart Study in 1988-1989. Incidence of hip fractures was recorded from 1988 to 1995. BMD at the hip, spine, and arm was assessed on 2 separate occasions (1988-1989 and 1992-1993). Comparisons between apo E genotype and BMD were made relative to E4 allele status (at least 1 epsilon4 allele compared with no epsilon4 allele). RESULTS: Individuals in the highest quartile of vitamin K intake (median: 254 microg/d) had a significantly lower fully adjusted relative risk (0.35; 95% CI: 0. 13, 0.94) of hip fracture than did those in the lowest quartile of intake (median: 56 microg/d). There were no associations between vitamin K intake and BMD in either men or women. No association was found between the E4 allele and BMD, and there were no significant interactions between the E4 allele and phylloquinone intake and BMD or hip fracture. CONCLUSIONS: Low vitamin K intakes were associated with an increased incidence of hip fractures in this cohort of elderly men and women. Neither low vitamin K intake nor E4 allele status was associated with low BMD.

Dietary vitamin K1 and stability of oral anticoagulation: proposal of a diet with constant vitamin K1 content.

Case reports cited in Medline or Biological Abstracts (1966-1996) were reviewed to evaluate the impact of vitamin K1 dietary intake on the stability of anticoagulant control in patients using coumarin derivatives. Reported nutrient-drug interactions cannot always be explained by the vitamin K1 content of the food items. However, metabolic data indicate that a consistent dietary intake of vitamin K is important to attain a daily equilibrium in vitamin K status. We report a diet that provides a stable intake of vitamin K1 equivalent to the current U.S. Recommended Dietary Allowance, using food composition data derived from high-performance liquid chromatography. Inconsistencies in the published literature indicate that prospective clinical studies should be undertaken to clarify the putative dietary vitamin K1-coumarin interaction. The dietary guidelines reported here may be used in such studies.

Skeletal functions of vitamin K-dependent proteins: not just for clotting anymore.

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.

Warfarin use and fracture risk.

Two recent studies examined the association between chronic use of warfarin, a vitamin K antagonist, and fracture rate among older women. Whereas one study reported no association, the other reported a significantly higher risk for vertebral and rib fractures among warfarin users compared with nonusers. The effect of vitamin K antagonists on age-related bone loss continues to be controversial.

Vitamin K: a practical guide to the dietary management of patients on warfarin.

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 anticoagulation 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 micrograms/day is the most acceptable practice for patients on warfarin therapy. Vitamin K composition data for commonly consumed foods are now available and may facilitate successful anticoagulation for patients being treated with warfarin.

Dietary fat consumption and health.

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

Assessment of phylloquinone and dihydrophylloquinone dietary intakes among a nationally representative sample of US consumers using 14-day food diaries.

OBJECTIVE: To estimate dietary intakes of phylloquinone and dihydrophylloquinone in a representative sample of the American population using 14-day food diaries. DESIGN: Vitamin K food composition data were applied to 14-day food diaries completed by a nationally representative sample of approximately 2,000 households that participated in a Market Research Corporation of America menu census survey between July 1991 and June 1992. Dietary intakes were estimated for phylloquinone and dihydrophylloquinone. SUBJECTS: Subjects were 4,741 men, women and children with demographic characteristics similar to those of the US census population. STATISTICAL ANALYSIS PERFORMED: Descriptive statistics and 2-sample t tests. RESULTS: Mean reported intakes of phylloquinone among adults increased with age. Men and women in the 18- to 44-year-old groups reported mean phylloquinone intakes below the current Recommended Dietary Allowance for vitamin K. Of all study participants, 99.3% reported consumption of dihydrophylloquinone during the 14 days of diet recording; reported intakes peaked before the age of 6 years; after the age of 6 years intakes were constant. APPLICATIONS: The Market Research Corporation of America data provide a reference range for dietary intakes of 2 forms of vitamin K in the US diet: phylloquinone and dihydrophylloquinone. Given the putative role of vitamin K in bone mineralization, low intakes of phylloquinone reported among young adults highlight the need to educate the US population about the requirement for and sources of vitamin K. The abundance of dihydrophylloquinone in the US diet suggests the need for study of its biological activity relative to phylloquinone.