Dietary Intakes of Community-Dwelling Adults in the United States across Older Adulthood: National Health and Nutrition Examination Survey 2015-March 2020.

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.

Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial.

BACKGROUND: Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease. METHODS: A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest. RESULTS: A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups. CONCLUSION: We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible.

Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults.

INTRODUCTION: Vitamin D purportedly protects against cognitive decline and dementia based on observational data using circulating 25-hydroxyvitamin D (25(OH)D). Little is known about vitamin D in the human brain and the association with dementia or neuropathology. METHODS: Decedents of the Rush Memory and Aging Project (n = 290) had vitamin D concentrations measured in four brain regions. Associations with cognitive and neuropathological outcomes were estimated using linear and logistic regression. RESULTS: The main form of vitamin D in all brain regions measured was 25(OH)D3 . Higher brain 25(OH)D3 concentrations were associated with a 25% to 33% lower odds of dementia or mild cognitive impairment (MCI) at the last visit before death (all P ≤ .031). However, brain 25(OH)D concentrations were not associated with any post-mortem neuropathology outcome studied. DISCUSSION: Higher brain 25(OH)D3 concentrations were associated with better cognitive function prior to death. Additional research is needed to clarify the specific mechanisms underlying this potentially protective relationship.

Vitamin D and Vitamin K Concentrations in Human Brain Tissue Are Influenced by Freezer Storage Time: The Memory and Aging Project.

BACKGROUND: Vitamins D and K, which are present in human brain, may have a role in neurodegenerative disease. OBJECTIVES: Given the interest in measuring nutrient concentrations in archived brain samples, it is important to evaluate whether freezer storage time affects these concentrations. Therefore, we evaluated differences in vitamin D and vitamin K concentrations in human brain samples stored for various lengths of time. METHODS: Postmortem brain samples were obtained from 499 participants in the Rush Memory and Aging Project (mean age 92 y, 72% female). Concentrations of vitamins D and K and their metabolites were measured in 4 regions (midtemporal cortex, midfrontal cortex, cerebellum, anterior watershed white matter) using LC-MS/MS and HPLC, respectively. The predominant forms were 25-hydroxycholecalciferol [25(OH)D3] and menaquinone-4 (MK4). ANOVA was used to determine if concentrations differed according to storage time. RESULTS: The geometric mean of the mean 25(OH)D3 concentration (across 4 regions) in brains stored for 1.1 to 6.0 y did not differ from that in brains stored ≤1.0 y (all P ≥ 0.37), whereas 25(OH)D3 in brains stored >6.0 y was 31-40% lower (P ≤ 0.003). MK4 had similar results, with the geometric mean MK4 concentration in the brains stored ≥9.0 y being 48-52% lower than those in brains stored ≤1.0 y (P ≤ 0.012). The 25(OH)D3 and MK4 concentrations were positively correlated across all 4 regions (all Spearman ρ ≥ 0.79, P < 0.001). CONCLUSIONS: 25(OH)D3 and MK4 appear to be stable in brain tissue from older adults stored at -80°C for up to 6 and 9 y, respectively, but not longer. Freezer storage time should be considered in the design and interpretation of studies using archived brain tissue.

Atorvastatin Decreases Renal Menaquinone-4 Formation in C57BL/6 Male Mice.

BACKGROUND: Menaquinone-4 (MK4), a vitamin K metabolite, is converted from phylloquinone through a process that requires intermediates of endogenous cholesterol production. Recent evidence suggests that MK4 is involved in kidney function. OBJECTIVE: The purpose of this study was to determine the effect of atorvastatin treatment on MK4 formation in young and old male mice. METHODS: C57BL/6 male mice (4-mo-old and 20-mo-old) were randomly assigned to either a diet containing 300 mg atorvastatin/kg with 3 mg phylloquinone/kg or a control diet containing 3 mg phylloquinone/kg for 8 wk. During week 8, all mice received deuterium-labeled phylloquinone in the diet. Labeled and unlabeled phylloquinone and MK4 in liver, kidney, brain, and intestine were measured by atmospheric pressure chemical ionization LC/MS. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene expression was quantified by reverse transcriptase-PCR. Tissue MK4 and phylloquinone concentrations were compared between atorvastatin treatment groups with use of general linear models. RESULTS: There was no age-treatment interaction on MK4 tissue concentrations. In atorvastatin-treated mice, total MK4 and percentage of deuterium-labeled MK4 in kidney were both approximately 45% lower compared to values in mice not given atorvastatin (all P < 0.05). MK4 concentrations did not differ between groups in any other tissue measured. CONCLUSION: In male mice, atorvastatin reduced endogenous MK4 formation in the kidney, but not other organs. These observations are consistent with our hypothesis that cholesterol metabolism is involved in the generation of MK4. Further research is needed to understand potential regulatory mechanisms and the unique functions of MK4 in the kidney.

Circulating Vitamin K Is Inversely Associated with Incident Cardiovascular Disease Risk among Those Treated for Hypertension in the Health, Aging, and Body Composition Study (Health ABC).

Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational studies found that low circulating phylloquinone (vitamin K-1) was associated with increased CAC progression, especially in persons treated for hypertension. It is unknown whether hypertension treatment modifies this putative role of vitamin K in clinical CVD risk.Objective: We determined the association between vitamin K status and incident clinical CVD in older adults in the Health ABC (Health, Aging, and Body Composition Study) and whether the association differed by hypertension treatment status.Methods: Plasma phylloquinone was measured in 1061 participants free of CVD (70-79 y of age, 58% women, 39% black). Plasma uncarboxylated MGP [(dp)ucMGP] was measured in a subset of 635 participants. Multivariate Cox models estimated the HR for incident CVD over 12.1 follow-up years. Effect modification by hypertension was tested with the use of interaction terms.Results: Neither low plasma phylloquinone (<0.2 nmol/L) nor elevated (dp)ucMGP (≥574 pmol/L) was significantly associated with incident CVD [respective HRs (95% CIs): 1.27 (0.75, 2.13) and 1.02 (0.72, 1.45)]. In participants treated for hypertension (n = 489; 135 events), low plasma phylloquinone was associated with higher CVD risk overall (HR: 2.94; 95% CI: 1.41, 6.13). In those with untreated hypertension (n = 153; 48 events) and without hypertension (n = 418; 92 events), low plasma phylloquinone was not associated with incident CVD. The association between high (dp)ucMGP did not differ by hypertension treatment status (P-interaction = 0.72).Conclusions: Vitamin K status was not significantly associated with CVD risk overall, but low plasma phylloquinone was associated with a higher CVD risk in older adults treated for hypertension. Additional evidence from larger clinical studies is needed to clarify the importance of vitamin K to CVD in persons treated for hypertension, a segment of the population at high risk of clinical CVD events.

Vitamin K-Dependent Protein Activity and Incident Ischemic Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Vitamin K-dependent proteins (VKDPs), which require post-translational modification to achieve biological activity, seem to contribute to thrombus formation, vascular calcification, and vessel stiffness. Whether VKDP activity is prospectively associated with incident cardiovascular disease has not been studied. APPROACH AND RESULTS: VKDP activity was determined by measuring circulating des-γ-carboxy prothrombin concentrations in a random sample of 709 multiethnic adults free of cardiovascular disease drawn from the Multi-Ethnic Study of Atherosclerosis (MESA). Lower des-γ-carboxy prothrombin concentrations reflect greater VKDP activity. Subjects were followed up for the risk of ischemic cardiovascular disease (coronary heart disease, stroke, and fatal cardiovascular disease) for 11.0 years of follow-up. A total of 75 first ischemic CVD events occurred during follow-up. The incidence of ischemic cardiovascular disease increased progressively across des-γ-carboxy prothrombin quartiles, with event rates of 5.9 and 11.7 per 1000 person-years in the lowest and highest quartiles. In analyses adjusted for traditional cardiovascular risk factors and measures of vitamin K intake, a doubling of des-γ-carboxy prothrombin concentration was associated with a 1.53 (95% confidence interval, 1.09-2.13; P=0.008) higher risk of incident ischemic cardiovascular disease. The association was consistent across strata of participants with diabetes mellitus, hypertension, renal impairment, and low vitamin K nutritional intake. CONCLUSIONS: In this sample of middle-aged and older adults, VKDP activity was associated with incident ischemic cardiovascular events. Further studies to understand the role of this large class of proteins in cardiovascular disease are warranted.

Vitamin D, Alzheimer's disease and related dementia.

Vitamin D has been proposed as a potential strategy to mitigate age-related cognitive decline and dementia, including Alzheimer's dementia, the predominant type of dementia. Rodent studies have provided insight into the potential mechanisms underlying the role of vitamin D in Alzheimer's disease and dementia. However, inconsistencies with respect to age, sex, and genetic background of the rodent models used poses some limitations regarding scientific rigor and translation. Several human observational studies have evaluated the association of vitamin D status with cognitive decline and dementia, and the results are conflicting. Randomized clinical trials of vitamin D supplementation have included cognitive outcomes. However, most of the available trials have not been designed specifically to test the effect of vitamin D on age-related cognitive decline and dementia, so it remains questionable how much additional vitamin D will improve cognitive performance. Here we evaluate the strengths and limitations of the available evidence regarding the role of vitamin D in AD, cognitive decline, dementia.

A Sensitive Method for Determination 1,25-Dihydroxyvitamin D3 in Human Brain using Ultra-Pressure Liquid Chromatography Tandem Mass Spectrometry.

The hormonally active form of vitamin D, 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], has been associated with neuroprotective effects in the brain, but has been difficult to measure in human brain tissue because of its low concentration. The aim of this study was to develop and validate a sensitive method to quantify 1,25(OH)2D3 in the human brain. Prior to analysis by the LC-MS/MS, the samples were derivatized with 4-phenyl-1,2,4-triazoline-3,5-dione. The method showed good linearity of 1,25(OH)2D3 over the physiological range (R 2 = 0.9998). The limit of detection was 2.5 pg/g, >10 times lower than the previously reported limit of detection. The average 1,25(OH)2D3 concentrations in 3 regions of human brain tissue samples were: anterior watershed 30.7 pg/g; mid-temporal cortex 19.2 pg/g; and cerebellum 18.5 pg/g. This validated method to quantify 1,25(OH)2D3 in human brain tissue can be applied to obtain information about its presence in various regions of the human brain associated with neurodegenerative diseases.

Dietary protein intake in midlife in relation to healthy aging - results from the prospective Nurses' Health Study cohort.

BACKGROUND: Protein intake plays an important role in maintaining the health status of older adults. However, few epidemiologic studies examined midlife protein intake in relation to healthy aging. OBJECTIVES: The objective of this study was to evaluate the long-term role of dietary protein intake in healthy aging among female participants in the prospective Nurses' Health Study (NHS) cohort. METHODS: We included 48,762 NHS participants aged <60 y in 1984. Total protein, animal protein, dairy protein (a subset of animal protein), and plant protein were derived from validated food frequency questionnaires. Healthy aging was defined as being free from 11 major chronic diseases, having good mental health, and not having impairments in either cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. We used multivariate logistic regression adjusted for lifestyle, demographics, and health status to estimate the odds ratios (ORs) and 95% confidence intervals for protein intake in relation to healthy aging. RESULTS: A total of 3721 (7.6%) NHS participants met our healthy aging definition. Protein intake was significantly associated with higher odds of healthy aging. The ORs (95% confidence intervals) per 3%-energy increment with healthy aging were 1.05 (1.01, 1.10) for total protein, 1.07 (1.02, 1.11) for animal protein, 1.14 (1.06, 1.23) for dairy protein, and 1.38 (1.24, 1.54) for plant protein. Plant protein was also associated with higher odds of absence of physical function limitations and good mental status. In substitution analyses, we observed significant positive associations for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein (ORs for healthy aging: 1.22-1.58 for 3% energy replacement with plant protein). CONCLUSIONS: Dietary protein intake, especially plant protein, in midlife, is associated with higher odds of healthy aging and with several domains of positive health status in a large cohort of female nurses.

Perspective: Promoting Healthy Aging through Nutrition: A Research Centers Collaborative Network Workshop Report.

Within 20 y, the number of adults in the United States over the age of 65 y is expected to more than double and the number over age 85 y is expected to more than triple. The risk for most chronic diseases and disabilities increases with age, so this demographic shift carries significant implications for the individual, health care providers, and population health. Strategies that delay or prevent the onset of age-related diseases are becoming increasingly important. Although considerable progress has been made in understanding the contribution of nutrition to healthy aging, it has become increasingly apparent that much remains to be learned, especially because the aging process is highly variable. Most federal nutrition programs and nutrition research studies define all adults over age 65 y as "older" and do not account for physiological and metabolic changes that occur throughout older adulthood that influence nutritional needs. Moreover, the older adult population is becoming more racially and ethnically diverse, so cultural preferences and other social determinants of health need to be considered. The Research Centers Collaborative Network sponsored a 1.5-d multidisciplinary workshop that included sessions on dietary patterns in health and disease, timing and targeting interventions, and health disparities and the social context of diet and food choice. The agenda and presentations can be found at https://www.rccn-aging.org/nutrition-2023-rccn-workshop. Here we summarize the workshop's themes and discussions and highlight research gaps that if filled will considerably advance our understanding of the role of nutrition in healthy aging.

Matrix Gla protein and the long-term incidence and progression of coronary artery and aortic calcification in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Matrix Gla protein (MGP) is an inhibitor of calcification that requires carboxylation by vitamin K for activity. The inactive form of MGP, dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP), has been associated with increased calcification. However, it is not known whether there is a longitudinal relationship between dephosphorylated-uncarboxylated matrix Gla protein levels and coronary and aortic calcification in large population cohorts. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) followed participants with serial cardiac computed tomography (CT) measures of vascular calcification. Dp-ucMGP was measured at baseline in a subset of participants who completed baseline and follow-up CTs approximately 10 years later and had available plasma specimens (n = 2663). Linear mixed effects models (LMMs) were used to determine the association of dp-ucMGP with the simultaneous incidence and progression of coronary artery, ascending thoracic aortic, or descending thoracic aortic calcification (CAC, ATAC, DTAC)]. RESULTS: For every one standard deviation (SD, 178 pmol/L) increment in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p < 0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p = 0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p < 0.001) AU/year. The association was stronger for DTAC in those ≥65 years and with diabetes. CONCLUSIONS: We found a positive association of the inactive form of matrix Gla protein, dp-ucMGP, and long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate dp-ucMGP as a calcification regulator and MGP as a possible therapeutic target to slow progression of calcification in the vasculature.

Lack of Consensus Between Measurements of Plasma Phylloquinone by Enzyme-Linked Immunosorbent assays and a Well-Validated High-Performance Liquid Chromatographic Method.

Enzyme-linked i2mmunosorbent assays (ELISAs) that measure circulating phylloquinone have become commercially available, but their validity is uncertain. The objective of this study was to compare plasma phylloquinone concentrations measured using two commercially available ELISAs with concentrations measured using a validated high-performance liquid chromatography (HPLC) assay in 108 samples obtained from participants in a depletion (∼10 mcg phylloquinone/d)-supplementation (∼500 mcg phylloquinone/d) study. The geometric mean of plasma phylloquinone measured with ELISA A was 0.70 nmol/L, 37% lower than that measured with HPLC. The mean of the ELISA B measures was 12.4 nmol/L, >700% higher than the HPLC measures. Plasma phylloquinone measured using HPLC was significantly lower during phylloquinone depletion than supplementation (0.4 ± 0.1 compared with 1.2 ± 0.2 nmol/L; P < 0.001). Neither of the two ELISAs detected any significant difference in plasma phylloquinone concentrations between depletion and supplementation (ELISA A, P = 0.76; ELISA B, P = 0.29). These findings reinforce the need to validate plasma phylloquinone assays as they become available. Curr Dev Nutr 2023;x:xx.

An Exploratory Case-Control Study on the Associations of Bacterially-Derived Vitamin K Forms with the Intestinal Microbiome and Obesity-Related Osteoarthritis.

Background: Evidence suggests that natural metabolites produced by intestinal microorganisms may have beneficial or harmful effects on osteoarthritis (OA). This could include menaquinones, which are bacterially-synthesized, biologically-active vitamin K forms abundant in the intestinal microbiome. Objectives: The overall goal of this study was to evaluate the association of intestinally-derived menaquinones with obesity-related OA. Methods: This case-control study used data and biospecimens derived from a subgroup of Johnston County Osteoarthritis Study participants. Fecal menaquinone concentrations and microbial composition were determined in 52 obese participants with hand and knee OA and 42 age- and sex-matched obese participants without OA. The inter-relationships among fecal menaquinones were evaluated using principal component analysis. The differences in alpha and beta diversities and microbial composition across menaquinone clusters were evaluated using ANOVA. Results: The samples were clustered into the following 3 groups: cluster 1 characterized by higher fecal menaquinone-9 and -10 concentrations, cluster 2 characterized by lower overall menaquinone concentrations, and cluster 3 characterized by higher menaquinone-12 and -13 concentrations. Overall, fecal menaquinone clusters did not differ between participants with or without OA (P = 0.707). Microbial diversity did not differ across the fecal menaquinone clusters (all F-test P > 0.12). However, the relative abundance of bacterial taxa differed among clusters, with higher abundance of Coprococcus, Prevotella, and Eggerthella in cluster 2 than in cluster 1; higher abundance of Oscillospira, Dorea, Eubacterium, and Bacteroides in cluster 3 than in cluster 1; and higher abundance of Prevotella, Sutterella, and Dorea in cluster 3 than in cluster 2 (all P < 0.001). Conclusion: Menaquinones were variable and abundant in the human gut, but the fecal menaquinone clusters did not differ with OA status. Although the relative abundance of specific bacterial taxa differed among fecal menaquinone clusters, the relevance of these differences with respect to vitamin K status and human health is uncertain.

Association of Vitamin K Status with Arterial Calcification and Stiffness in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort.

Background: Arterial calcification and stiffness are common in people with chronic kidney disease (CKD). Higher vitamin K status has been associated with less arterial calcification and stiffness in CKD in cross-sectional studies. Objectives: To determine the association of vitamin K status with coronary artery calcium (CAC) and arterial stiffness [pulse wave velocity (PWV)] at baseline and over 2-4 follow-up years in adults with mild-to-moderate CKD. Methods: Participants (n = 2722) were drawn from the well-characterized Chronic Renal Insufficiency Cohort. Two vitamin K status biomarkers, plasma phylloquinone and plasma dephospho-uncarboxylated matrix gla protein [(dp)ucMGP], were measured at baseline. CAC and PWV were measured at baseline and over 2-4 y of follow-up. Differences across vitamin K status categories in CAC prevalence, incidence, and progression (defined as ≥100 Agatston units/y increase) and PWV at baseline and over follow-up were evaluated using multivariable-adjusted generalized linear models. Results: CAC prevalence, incidence, and progression did not differ across plasma phylloquinone categories. Moreover, CAC prevalence and incidence did not differ according to plasma (dp)ucMGP concentration. Compared with participants with the highest (dp)ucMGP (≥450 pmol/L), those in the middle category (300-449 pmol/L) had a 49% lower rate of CAC progression (incidence rate ratio: 0.51; 95% CI: 0.33, 0.78). However, CAC progression did not differ between those with the lowest (<300 pmol/L) and those with the highest plasma (dp)ucMGP concentration (incidence rate ratio: 0.82; 95% CI: 0.56, 1.19). Neither vitamin K status biomarker was associated with PWV at baseline or longitudinally. Conclusions: Vitamin K status was not consistently associated with CAC or PWV in adults with mild-to-moderate CKD.

25-hydroxyvitamin D status and change in physical performance and strength in older adults: the Health, Aging, and Body Composition Study.

Low 25-hydroxyvitamin D (25(OH)D) concentrations are common among older adults and are associated with poorer physical performance and strength, but results from longitudinal studies have been inconsistent. The 25(OH)D threshold for physical performance and strength was determined, and both cross-sectional and longitudinal associations between 25(OH)D and physical performance and strength were examined, in men and women aged 71-80 years from the Health, Aging, and Body Composition Study (n = 2,641). Baseline serum 25(OH)D was measured in 1998-1999, and physical performance and strength were measured at baseline and at 2- and 4-year follow-up. Piecewise regression models were used to determine 25(OH)D thresholds. Linear regression and mixed models were used to examine cross-sectional and longitudinal associations. The 25(OH)D thresholds were 70-80 nmol/L for physical performance and 55-70 nmol/L for strength. Participants with 25(OH)D <50 nmol/L had poorer physical performance at baseline and at 2- and 4-year follow-up than participants with 25(OH)D ≥75 nmol/L (P < 0.01). Although physical performance and strength declined over 4 years of follow-up (P < 0.0001), in general, the rate of decline was not associated with baseline 25(OH)D. Older adults with low 25(OH)D concentrations had poorer physical performance over 4 years of follow-up, but low 25(OH)D concentrations were not associated with a faster rate of decline in physical performance or strength.

Circulating phylloquinone concentrations of adults in the United States differ according to race and ethnicity.

Differences in micronutrient status are reported to contribute to racial and ethnic differences in chronic diseases. Diseases related to vitamin K are reported to differ by race and ethnicity, but it is unclear if circulating vitamin K concentrations similarly differ. We examined racial and ethnic differences in serum phylloquionone (K1) in the Multiethnic Study of Atherosclerosis (MESA) (mean ± SD age = 62 ± 10 y; 52% female; 262 white, 180 African American, 169 Hispanic, 93 Chinese American). Overall, 25% had serum K1 <0.1 nmol/L (the lower limit of detection). The prevalence of low serum K1 was 4% in Chinese Americans compared with 24% of whites, 29% of African Americans, and 33% of Hispanics. Compared with whites, Chinese Americans were significantly less likely to have serum K1 <0.1 nmol/L [OR (95% CI): 0.23 (0.09-0.23), adjusted for serum TG, K1 intake, age, sex, BMI, smoking, total cholesterol, site, season, and lipid-lowering medication use]. African Americans and Hispanics had similar odds to whites for having serum K1 <0.1 nmol/L [OR(95% CI): 1.30 (0.79-2.15) and 1.19 (0.66-2.15), respectively; fully adjusted]. In participants with detectable concentrations (n = 523), (natural log) serum K1 was higher in the Chinese Americans compared with whites, African Americans, and Hispanics (geometric mean ± SEM = 2.2 ± 0.1 nmol/L vs. 1.2 ± 0.1 nmol/L, 1.5 ± 0.1 nmol/L, and 1.1 ± 0.1 nmol/L, respectively, adjusted for serum TG, K1 intake, and additional covariates; all P < 0.001). These findings suggest circulating K1 differs by race and ethnicity in U.S. adults, especially among those of Chinese American descent, which merits consideration in the design and interpretation of future population-based and clinical studies of vitamin K and related diseases.

Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats.

Phylloquinone (PK) is converted into menaquinone-4 (MK-4) via side chain removal-addition. Stable isotope use is an effective approach to identify the tissue location of this conversion, which is currently unknown. Following a 14-d PK-deficient diet, male Fischer 344 rats (8 mo; n = 15) were fed 1.6 mg deuterium-labeled PK (L-PK) per kg diet for 0 (control), 1 d (PK-1d), and 7 d (PK-7d). Both L-PK and deuterium-labeled MK-4 (L-MK-4) were detected in tissues in PK-1d and PK-7d, although the results varied. Whereas some tissues had an overall increase in MK-4 in response to L-PK, total brain, testes, and fat MK-4 concentrations did not. In contrast, L-MK-4 concentrations increased in all 3 tissues. The deuterium label was found only on the L-MK-4 naphthoquinone ring, confirming the need for side chain removal for the formation of MK-4. Labeled menadione (MD) was detected in urine and serum in PK-1d and PK-7d, confirming its role as an intermediate. A Caco-2 cell monolayer model was used to study the role of the enterocytes in the conversion process. Neither MK-4 nor MD was detected in Caco-2 cells treated with PK. However, when Caco-2 cells were treated with MD, MK-4 was formed. Similarly, MK-4 was formed in response to MD-treated 293T kidney cells, but not HuH7 liver cells. These data demonstrate that MK-4 is the predominant form of vitamin K in multiple tissues, but there appears to be a tissue-specific regulation for the conversion of PK to MK-4.

Plasma alkylresorcinols, biomarkers of whole-grain intake, are related to lower BMI in older adults.

Alkylresorcinols (AR) are phenolic lipids found in the bran fraction of whole-grain wheat, rye, and barley. In intervention studies, plasma AR concentration increased in response to greater intakes of whole grain, wheat, and rye. This study examined the cross-sectional associations between plasma AR and habitual whole-grain intake, BMI, and metabolic risk factors in 407 free-living older adults (166 men and 241 women; aged 60-81y; median BMI: 27 kg/m(2)). Plasma AR were measured by liquid chromatography-tandem MS, and whole-grain intakes were estimated by using an FFQ. After adjustment for fasting TG concentrations, median plasma AR concentrations across quartile categories of AR were 5, 14, 27, and 62 nmol/L, respectively. Spearman correlation coefficients between plasma AR and whole-grain wheat-rich foods and total bran intake were 0.31 and 0.27, respectively (both P < 0.0001). After adjustment for multiple covariates, the geometric means of BMI in the lowest and highest quartile category of plasma AR were 27.6 and 26.7 kg/m(2), respectively (P-trend = 0.04). No associations were observed between plasma AR and glucose and insulin. Our study shows a dose-dependent relationship between whole-grain intake and plasma AR and confirms the previously observed inverse relationship between whole-grain intake and BMI using an independent biomarker of whole-grain wheat intake.