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Background: Dietary guidance is set on the basis of age and life stage and defines older adults as ≥60 y. Yet, little is known about if and/or how diet quality differs beyond the age of 60., Objective: The objective of this study was to compare the dietary intakes of 60-69 (n = 2079), 70-79 (n = 1181), and 80+ y old (n = 644) noninstitutionalized men and women in the United States using the Healthy Eating Index 2015 (HEI) and the What We Eat in America food categories., Methods: Data were obtained from National Health and Nutrition Examination Survey 2015-2016 and 2017-March 2020. HEI and component scores were calculated using the population ratio method. Population estimates for dietary intake were calculated as the average reported over 2 separate nonconsecutive 24-h dietary recalls., Results: In men and women, the reported energy intake was lower among the 80+ y olds (kcal/d men-80+: 1884 ± 30, 70-79: 2022 ± 33, 60-69: 2142 ± 39; women-80+: 1523 ± 36; 70-79: 1525 ± 33, 60-69: 1650 ± 25; P-trend < 0.001). Total HEI scores did not differ significantly across the 3 age categories, but the 80+ y olds had significantly lower scores for the green vegetables and beans component than the 60-69 y olds [men-mean (95% confidence interval): 2.0 (1.5, 2.5) compared with 3.4 (2.6, 4.1); women-2.3 (1.8, 2.8) compared with 4.4 (3.7, 5.0)]. In women, the percentage of daily calories from protein was significantly lower in the 80+ y olds than in the 60-69 and 70-79 y olds (12.9% ± 0.6%, compared with 17.0% ± 0.9% and 15.6% ± 0.6%, respectively). Protein intake did not differ significantly among the 3 age groups in men. The 80+ y old men and women reported consuming a significantly higher percentage of calories from snacks and sweets compared with the 60-69 y olds (men-80+: 18.1% ± 0.8%, 60-69: 15.4% ± 0.7%; women-80+: 19.6% ± 0.8%, 60-69: 15.5% ± 0.7%)., Conclusion: The diet of 80+ y olds differed from that of 60-69 y olds in some key components, including energy, snacks and sweets, protein, and green vegetables. Future research is needed to determine if there are health-related consequences to these differences., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Chow diet is used in the majority of rodent studies and, although assumed to be standardized for dietary source and nutritional contents, it varies widely across commercial formulations. Similarly, current approaches to study aging in rodents involve a single-diet formulation across the lifespan and overlook age-specific nutritional requirements, which may have long-term effects on aging processes. Together, these nutrition-based disparities represent major gaps in geroscience research, affecting the interpretation and reproducibility of the studies. This perspective aims to raise awareness on the importance of rodent diet formulation and proposes that geroscientists include detailed descriptions of all experimental diets and feeding protocols. Detailed reporting of diets will enhance rigor and reproducibility of aging rodent studies and lead to more translational outcomes in geroscience research., (© 2023. The Author(s).)

By 2060, the number of adults aged ≥65 y is expected to double, and the ≥85 y segment of the population is expected to triple in the United States. US federal nutrition guidance is based on the premise that healthy diets contribute to delaying the onset and progression of many age-related diseases and disability. Yet, little is known about the dietary intakes or nutritional needs across the older adulthood age span. This review aims to identify community-based cohorts that collected information on dietary intake of adults ≥65 y in the United States. Thirty-two cohorts met all inclusion criteria. We summarized information on the cohorts' design, demographics, and diet assessment. We also identified key gaps in the existing databases that, if filled, could enhance their utility to address certain research questions. This review serves as a valuable inventory of cohorts that can be leveraged to answer key questions about the diet and nutritional needs of the oldest old, who represent the fastest growing segment of the population in the United States., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: To determine whether dietary intake of flavonols is associated with Alzheimer dementia., Methods: The study was conducted among 921 participants of the Rush Memory and Aging Project (MAP), an ongoing community-based, prospective cohort. Participants completed annual neurologic evaluations and dietary assessments using a validated food frequency questionnaire., Results: Among 921 MAP participants who initially had no dementia in the analyzed sample, 220 developed Alzheimer dementia. The mean age of the sample was 81.2 years (SD 7.2), with the majority (n = 691, 75%) being female. Participants with the highest intake of total flavonols had higher levels of education and more participation in physical and cognitive activities. In Cox proportional hazards models, dietary intakes of flavonols were inversely associated with incident Alzheimer dementia in models adjusted for age, sex, education, APOE ɛ4, and participation in cognitive and physical activities. Hazard ratios (HRs) for the fifth vs first quintiles of intake were as follows: for total flavonol, 0.52 (95% confidence interval [CI], 0.33-0.84); for kaempferol, 0.49 (95% CI, 0.31-0.77); for myricetin, 0.62 (95% CI, 0.4-0.97); and for isorhamnetin, 0.62 (95% CI, 0.39-0.98). Quercetin was not associated with Alzheimer dementia (HR, 0.69; 95% CI, 0.43-1.09)., Conclusion: Higher dietary intakes of flavonols may be associated with reduced risk of developing Alzheimer dementia., (© 2020 American Academy of Neurology.)

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.

Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined. Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation. Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8. Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation. Conclusion: Menaquinone concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear. This trial was registered at clinicaltrials.gov as NCT01902394., (© 2017 American Society for Nutrition.)

Background: There has been limited characterization of biological variables that impact vitamin K metabolism. This gap in knowledge can limit the translation of data obtained from preclinical animal studies to future human studies., Objective: The purpose of this study was to determine the effects of diet, sex, and housing on serum, tissue, and fecal vitamin K concentrations and gene expression in C57BL6 mice during dietary vitamin K manipulation., Methods: C57BL6 4-mo-old male and female mice were randomly assigned to conventional or suspended-wire cages and fed control [1400 ± 80 μg phylloquinone (PK)/kg] or deficient (31 ± 0.45 μg PK/kg) diets for 28 d in a factorial design. PK and menaquinone (MK) 4 plasma and tissue concentrations were measured by HPLC. Long-chain MKs were measured in all matrices by LC-atmospheric pressure chemical ionization-mass spectrometry. Gene expression was quantified by reverse transcriptase-polymerase chain reaction in the liver, brain, kidney, pancreas, and adipose tissue., Results: Male and female mice responded differently to dietary manipulation in a tissue-dependent manner. In mice fed the control diet, females had ∼3-fold more MK4 in the brain and mesenteric adipose tissue than did males and 100% greater PK concentrations in the liver, kidney, and mesenteric adipose tissue than did males. In mice fed the deficient diet, kidney MK4 concentrations were ∼4-fold greater in females than in males, and there were no differences in other tissues. Males and females differed in the expression of vitamin K expoxide reductase complex 1 (Vkorc1) in mesenteric adipose tissue and the pancreas and ubiA domain-containing protein 1 (Ubiad1) in the kidney and brain. There was no effect of housing on serum, tissue, or fecal concentrations of any vitamin K form., Conclusions: Vitamin K concentrations and expression of key metabolic enzymes differ between male and female mice and in response to the dietary PK concentration. Identifying factors that may impact study design and outcomes of interest is critical to optimize study parameters examining vitamin K metabolism in animal models., (© 2016 American Society for Nutrition.)

Background: Emerging evidence supports novel roles for vitamin K in cardiometabolic health, some of which may be unique to the bacterially synthesized vitamin K forms known as menaquinones. However, factors influencing menaquinone biosynthesis by the gut microbiota and associations with cardiometabolic health have not been examined., Objective: The objective of this study was to identify associations between fecal menaquinone profiles, gut microbiota composition, and biomarkers of cardiometabolic health., Design: The menaquinone profile and gut microbiota structure were periodically measured in fecal samples collected from 77 overweight Chinese adults who consumed a prescribed diet previously shown to alter gut microbiota composition and to improve cardiometabolic biomarkers., Results: Covariance among menaquinones within individual fecal samples partitioned individuals into 2 distinct groups, herein introduced as menaquinotypes of the human gut. Menaquinotypes were characterized by differences in menaquinone (MK) 5 and MK9-MK13 and differences in the relative abundance of several operational taxonomic units (OTUs) delineated at the species level, predominantly within the genera Prevotella spp. and Bacteroides spp. Fecal MK4, MK6, and MK8 decreased during the intervention (P < 0.05); and longitudinal changes in the relative abundance of >100 OTUs were associated with altered fecal content of ≥1 individual menaquinone. The strongest and most consistent relations were between Prevotella spp. and MK5 and MK11-MK13, between Bacteroides spp. and MK9 and MK10, and between Escherichia/Shigella spp. and MK8. Neither individual menaquinones nor menaquinotypes were longitudinally associated with markers of glycemia, insulin resistance, or inflammation., Conclusions: These findings suggest that variability in fecal menaquinone content is predominantly determined by relatively few genera within the gut microbiota and that diet-mediated alterations in gut microbiota composition may provide a feasible approach for altering gut menaquinone content. This trial was registered at the Chinese Clinical Trials Registry as ChiCTR-TRC-09000353., (© 2015 American Society for Nutrition.)

Foods high in dietary fiber may play an important role in regulating body weight. Few observational studies have examined the relationship between dietary fiber from different sources and body fat in older adults. Our objectives were to examine the associations among grain intake (whole and refined), dietary fiber and fiber sources, and body fat among older adults. We used data from 434 free-living adults (177 men and 257 women) aged between 60 and 80 y. Dietary intake was estimated from a 126-item semiquantitative FFQ. Percent body fat and percent trunk fat mass were measured by whole-body dual-energy X-ray absorptiometry. After adjustment for covariates, whole-grain intake was inversely associated with BMI [26.8 kg/m(2) (25.7-28.1) vs. 25.8 kg/m(2) (24.6-27.1), (95% CI); P-trend = 0.08], percent body fat [34.5% (32.7-36.3) vs. 32.1% (30.1-34.1); P-trend = 0.02], and percent trunk fat mass [43.0% (40.4-45.5) vs. 39.4% (36.7-42.1); P-trend = 0.02] in the lowest compared with the highest quartile category of whole-grain intake. Refined grain intake was not associated with any measure of body fat distribution. Cereal fiber was inversely associated with BMI [27.3 kg/m(2) (26.1-28.6) vs. 25.4 kg/m(2) (24.3-26.7); P-trend = 0.012], percent body fat [34.7% (32.8-36.6) vs. 31.5% (29.4-33.5); P-trend = 0.004], and percent trunk fat mass [42.8% (40.2-45.4) vs. 37.8% (35.0-40.6); P-trend = 0.001]. No significant association was observed between intakes of total fiber, vegetable or fruit fiber, and body composition measurements. Higher intakes of cereal fiber, particularly from whole-grain sources, are associated with lower total percent body fat and percent trunk fat mass in older adults.

Background: Limited evidence suggests that vitamin K may have a beneficial role in glucose homeostasis. No observational data exist on the associations between vitamin K intake and insulin sensitivity., Objective: We aimed to examine associations between vitamin K intake and measures of insulin sensitivity and glycemic status in men and women aged 26-81 y., Design: We assessed the cross-sectional associations of self-reported phylloquinone (vitamin K(1)) intake with insulin sensitivity and glycemic status in the Framingham Offspring Cohort. Dietary and supplemental phylloquinone intakes were assessed by using a food-frequency questionnaire. Insulin sensitivity was measured by fasting and 2-h post-oral-glucose-tolerance test (OGTT) insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulin sensitivity index (ISI(0,120)). Glycemic status was assessed by fasting and 2-h post-OGTT glucose and glycated hemoglobin (HbA(1c))., Results: Higher phylloquinone intake was associated with greater insulin sensitivity and glycemic status, as measured by 2-h post-OGTT insulin and glucose and ISI(0,120), after adjustment for age, sex, waist circumference, lifestyle characteristics, and diet quality [2-h post-OGTT insulin: lowest and highest quintile, 81.0 and 72.7 microU/mL, respectively (P for trend = 0.003); 2-h post-OGTT glucose: 106.3 and 101.9 mg/dL, respectively (P for trend = 0.009); ISI(0,120): 26.3 and 27.3 mg L(2)/mmol mU min (P for trend = 0.009)]. Phylloquinone intake was not associated with fasting insulin and glucose concentrations, HOMA-IR, or HbA(1c)., Conclusion: Our findings support a potential beneficial role for phylloquinone in glucose homeostasis in men and women.

Phylloquinone, the primary dietary form of vitamin K, is converted to menaquinone-4 (MK-4) in certain tissues. MK-4 may have tissue-specific roles independent of those traditionally identified with vitamin K. Fischer 344 male rats of different ages (2, 12, and 24 mo, n = 20 per age group) were used to compare the conversion of phylloquinone to MK-4 with an equivalent dose of another dietary form of vitamin K, 2',3'-dihydrophylloquinone. Rats were age- and diet-group pair-fed phylloquinone (198 +/- 9.0 microg/kg diet) or dihydrophylloquinone (172 +/- 13.0 microg/kg diet) for 28 d. MK-4 was the primary form of vitamin K in serum, spleen, kidney, testes, bone marrow, and brain myelin fractions, regardless of age group. MK-4 concentrations were significantly lower in kidney, heart, testes, cortex (myelin), and striatum (myelin) in the dihydrophylloquinone diet group compared with the phylloquinone diet group (P < 0.05). The MK-4 concentrations in 2-mo-old rats were lower in liver, spleen, kidney, heart, and cortex (myelin) but higher in testes compared with 24-mo-old rats (P < 0.05). However, there were no age-specific differences in MK-4 concentrations among the rats fed the 2 diets. These data suggest that dihydrophylloquinone, which differs from phylloquinone in its side phytyl chain, is absorbed but its intake results in less MK-4 in certain tissues. Dihydrophylloquinone may be used in models for the study of tissue-specific vitamin K deficiency.

The physiological function and putative health roles of vitamin K-dependent proteins now extend beyond their classical role in hemostasis and include bone mineralization, arterial calcification, apoptosis, phagocytosis, growth control, chemotaxis, and signal transduction. Current assessments of vitamin K status do not reflect the variety of molecular forms of vitamin K. We assessed whether urinary excretion of 2-methyl-3-(5'-carboxy-3'-methyl-2'-pentenyl)-1,4-naphthoquinone (7C-aglycone) and 2-methyl-3-(3'-3'-carboxymethylpropyl)-1,4-naphthoquinone (5C-aglycone), vitamin K metabolites common to both phylloquinone and the menaquinone series, reflect dietary vitamin K intake. In a randomized crossover study, 9 adults resided in a metabolic unit for two 30-d periods separated by a free-living period of > or = 4 wk. During each residency, subjects consumed 3 sequential diets: a control diet (93 microg phylloquinone/d) for 5 d, a phylloquinone-restricted diet (11 microg/d) for 15 d, followed by a randomly assigned repletion diet for 10 d with either phylloquinone (206 microg/d) or dihydrophylloquinone (240 microg/d). During the second residency, the alternative repletion diet was assigned. Urinary excretion of the 5C- and 7C-aglycones was measured in sequential 24-h collections. The 5C-aglycone accounted for approximately 75% of total excretion and declined in response to phylloquinone restriction (P = 0.001) to approximately 30% of that during the control diet period. Repletion with phylloquinone and dihydrophylloquinone doubled the excretion rate of the major 5C-aglycone by 24 h (P < 0.001), and tripled excretion by 4 d. There was a linear relationship between the logarithm of total urinary excretion and dietary vitamin K intake (r = 0.699, P < 0.001). We conclude that the urinary excretion of vitamin K metabolites reflects dietary phylloquinone intake and offers the first candidate marker of global vitamin K status.

Background: Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin., Aim of the Study: To determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular disease., Methods: Recent and usual food intakes were assessed in 115 patients receiving warfarin; and corresponding plasma phylloquinone (vitamin K(1)), serum triglyceride concentrations, prothrombin time (PT), and International Normalized Ratio (INR) were determined. A factor analysis was used to examine the association of specific foods and biochemical variables with anticoagulant data., Results: Mean age was 59 +/- 15 years. Inadequate anticoagulation, defined as values of INR 2 or 3, was found in 48% of the patients. Soybean oil and kidney beans were the primary food sources of phylloquinone intake. Factor analysis yielded four separate factors, explaining 56.4% of the total variance in the data set. The factor analysis revealed that intakes of kidney beans and soybean oil, 24-h recall of phylloquinone intake, PT and INR loaded significantly on factor 1. Triglycerides, PT, INR, plasma phylloquinone, and duration of anticoagulation therapy loaded on factor 3., Conclusions: Fluctuations in phylloquinone intake, particularly from kidney beans, and plasma phylloquinone concentrations were associated with variation in measures of anticoagulation (PT and INR) in a Brazilian group of patients with vascular disease.

The purpose of this study was to determine the contents of three forms of vitamin K [phylloquinone, dihydrophylloquinone, and menaquinone-4 (MK-4)] in representative samples (including different samples within the same food category) of meat (n = 128), dairy and eggs (n = 24), and fast foods (n = 169) common to the U.S. diet. The findings of our analysis indicate that no single food item in these categories is a rich dietary source of any one form of vitamin K. However, these foods are often consumed in large quantities; hence, they may be of importance in overall contribution to total vitamin K intake. The presence of MK-4 in meat, eggs, and dairy foods could be important as physiologic functions unique to MK-4 are identified.

Commercial hydrogenation results in the formation of trans fatty acids. An unintended consequence of the hydrogenation process is conversion of phylloquinone (vitamin K1) to dihydrophylloquinone. Plasma dihydrophylloquinone concentrations have yet to be characterized in population-based studies. Dietary determinants of plasma dihydrophylloquinone were estimated using a semi-quantitative food frequency questionnaire in 803 men and 913 women in the Framingham Offspring Study. Geometric mean dihydrophylloquinone intake was 21.3 (95 % CI 20.4, 22.3) microg/d in men and 19.4 (95 % CI 18.5, 20.2) microg/d in women. Detectable (>0.05 nmol/l) plasma dihydrophylloquinone concentrations were measured in 41 % and 30 % of men and women, respectively. The multivariate odds ratio (OR) of detectable plasma dihydrophylloquinone from the lowest to the highest quartile category of dihydrophylloquinone intake were 1 (referent), 1.13 (95 % CI 0.83, 1.53), 1.66 (95 % CI 1.21, 2.26) and 1.84 (95 % CI 1.31, 2.58), P for trend <0.001, adjusted for sex, age, body mass index, triacylglycerols, season and energy intake. Higher trans fatty acid intake was associated with higher multivariate OR for detectable plasma dihydrophylloquinone (OR comparing extreme quartiles 2.41 (95 % CI 1.59, 3.64), P for trend <0.001). There were limitations in the use of plasma dihydrophylloquinone, evident in the high proportion of the population that had non-detectable dihydrophylloquinone concentrations. Despite this caveat, higher plasma dihydrophylloquinone was associated with higher dihydrophylloquinone intake and higher trans fatty acid intake.

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. .

Assessment of vitamin K dietary intakes has been limited by incomplete vitamin K food composition data for the US food supply. The phylloquinone (vitamin K(1)) concentrations of nuts (n=76) and fruits (n=215) were determined by high-performance liquid chromatography. Each sample represented a composite of units obtained from 12 to 24 outlets, which provided geographic representation of the US food supply. With the exception of pine nuts and cashews, which contain 53.9 and 34.8 microg of phylloquinone per 100 g of nut, respectively, nuts are not important dietary sources of vitamin K. Similarly, most fruits are not important sources of vitamin K, with the exception of some berries, green fruits, and prunes. Menu planning for patients on warfarin can include a healthy diet including fruits and nuts without compromising the stability of their oral anticoagulation therapy.

Biological markers indicative of poor vitamin K status have been associated with a greater risk for hip fracture in older men and women. However, the dietary phylloquinone intake required to achieve maximal carboxylation of hepatic and extrahepatic vitamin K-dependent proteins is not known. In an 84-d study in a metabolic unit, 21 older (60-80 y) women were fed a phylloquinone-restricted diet (18 micro g/d) for 28 d, followed by stepwise repletion of 86, 200 and 450 micro g/d of phylloquinone. Plasma phylloquinone, urinary gamma-carboxyglutamic acid excretion and gamma-carboxylation of hepatic (prothrombin) and extrahepatic proteins (osteocalcin) decreased in response to phylloquinone restriction (P < 0.001), demonstrating the production of subclinical vitamin K deficiency. The gamma-carboxylation of prothrombin was restored to normal levels in response to phylloquinone supplementation at 200 micro g/d. In contrast, all other biochemical markers of vitamin K status remained below normal levels after short-term supplementation of up to 450 micro g/d of phylloquinone. These data support previous observations in rats that hepatic vitamin K-dependent proteins have preferential utilization of phylloquinone in response to phylloquinone dietary restriction. Moreover, our findings suggest that the current recommended Adequate Intake levels of vitamin K (90 micro g/d) in women do not support maximal osteocalcin gamma-carboxylation in older women.

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.

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.

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.

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.

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.

The current daily recommended dietary allowance for vitamin K is 1 microg/kg. Reliable measurements of vitamin K content in foods are now available, and data from 11 studies of vitamin K intake indicate that the mean intake of young adults is approximately 80 microg phylloquinone/d and that older adults consume approximately 150 microg/d. The vitamin K concentration in most foods is very low (<10 microg/100 g), and the majority of the vitamin is obtained from a few leafy green vegetables and four vegetable oils (soybean, cottonseed, canola and olive) that contain high amounts. Limited data indicate that absorption of phylloquinone from a food matrix is poor. Hydrogenated oils also contain appreciable amounts of 2', 3'-dihydrophylloquinone of unknown physiological importance. Menaquinones absorbed from the diet or the gut appear to provide only a minor portion of the human daily requirement. Measures of the extent to which plasma prothrombin or serum osteocalcin lack essential gamma-carboxyglutamic acid residues formed by vitamin K action, or the urinary excretion of this amino acid, provide more sensitive measures of vitamin K status than measures of plasma phylloquinone or insensitive clotting assays.

Dietary intakes of retinol equivalents, alpha-tocopherol equivalents, vitamin D and phylloquinone were estimated from three sets of 4-d weighed diet records and compared to three corresponding fasting plasma concentrations of retinol, 25-hydroxyvitamin D, alpha-tocopherol, and phylloquinone measured in 34 healthy adults over 20 wk. The magnitude of the correlation between dietary vitamin intake and its corresponding biochemical measure is in part determined by the reproducibility of each of the measures, so within-to-between subject variance ratios were calculated for both dietary intakes and plasma concentrations. Phylloquinone was the only fat-soluble vitamin with a significant correlation between dietary intake and fasting plasma concentration (r = 0.51, P = 0.004). This correlation improved with an increase in both the number of independent diet records and independent plasma measures. Of the dietary intake measures, all the fat-soluble vitamins had greater within than between subject variance, with the highest measured for phylloquinone (6.86:1). Of the plasma measures, only phylloquinone had a within-to-between subject variance ratio greater than one (5.36:1). Comparisons across age and sex for dietary intake and plasma concentrations differed in pattern among the fat-soluble vitamins.

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.

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.

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.

Objective: To examine the relationship between dietary phylloquinone intake and vitamin K status of postmenopausal Caucasian women., Design: Cross-sectional study, in which dietary intake was estimated using weighed record techniques and vitamin K status was measured by a single plasma phylloquinone concentration and 24-h urinary gamma-carboxyglutamic acid (Gla) excretion., Setting: The metabolic research unit at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA., Subjects: 402 healthy postmenopausal Caucasian women who were participating in a randomized trial to determine the effect of calcium supplementation on bone loss. Of the original group, 362 had complete weighed diet records, 358 had corresponding plasma phylloquinone concentrations, and 346 had corresponding urinary Gla measurements., Results: There was a significant correlation (r = 0.13, P = 0.01) between total dietary intake of phylloquinone (geometric mean = 89 micrograms/day) and plasma phylloquinone levels (mean = 1.12 nmol/l). Dietary intake was neither correlated with urinary Gla excretion (mean = 4.0 mumol/mmol creatinine) nor did it vary by season. The ratio of intra- to interindividual variance in phylloquinone intake was 2.6, from which it was estimated that 5 days of independent recording is necessary to estimate true usual dietary intake, assuming a correlation of 0.8., Conclusions: A weighed record has the potential to be a reliable method for estimating dietary intakes of vitamin K which relate to plasma phylloquinone levels used as an indicator of vitamin K status in postmenopausal Caucasian women.