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Background: Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration., Objective: We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zinc-deficient nursing home elderly., Design: This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged ≥65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc <70 μg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response., Results: Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, in the zinc group than in the placebo group (P = 0.007) when baseline zinc concentrations were controlled for. In addition, controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with ≤60 μg serum Zn/dL failed to increase their serum zinc to ≥70 μg/dL. Zinc supplementation also significantly increased anti-CD3/CD28 and phytohemagglutinin-stimulated T cell proliferation, and the number of peripheral T cells (P < 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in the number of T cells., Conclusions: Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations. The increase in serum zinc concentration was associated with the enhancement of T cell function mainly because of an increase in the number of T cells., (© 2016 American Society for Nutrition.)

Background: Golden Rice (GR) has been genetically engineered to be rich in β-carotene for use as a source of vitamin A., Objective: The objective was to compare the vitamin A value of β-carotene in GR and in spinach with that of pure β-carotene in oil when consumed by children., Design: Children (n = 68; age 6-8 y) were randomly assigned to consume GR or spinach (both grown in a nutrient solution containing 23 atom% ²H₂O) or [²H₈]β-carotene in an oil capsule. The GR and spinach β-carotene were enriched with deuterium (²H) with the highest abundance molecular mass (M) at M(β-C)+²H₁₀. [¹³C₁₀]Retinyl acetate in an oil capsule was administered as a reference dose. Serum samples collected from subjects were analyzed by using gas chromatography electron-capture negative chemical ionization mass spectrometry for the enrichments of labeled retinol: M(retinol)+4 (from [²H₈]β-carotene in oil), M(retinol)+5 (from GR or spinach [²H₁₀]β-carotene), and M(retinol)+10 (from [¹³C₁₀]retinyl acetate)., Results: Using the response to the dose of [¹³C₁₀]retinyl acetate (0.5 mg) as a reference, our results (with the use of AUC of molar enrichment at days 1, 3, 7, 14, and 21 after the labeled doses) showed that the conversions of pure β-carotene (0.5 mg), GR β-carotene (0.6 mg), and spinach β-carotene (1.4 mg) to retinol were 2.0, 2.3, and 7.5 to 1 by weight, respectively., Conclusions: The β-carotene in GR is as effective as pure β-carotene in oil and better than that in spinach at providing vitamin A to children. A bowl of ~100 to 150 g cooked GR (50 g dry weight) can provide ~60% of the Chinese Recommended Nutrient Intake of vitamin A for 6-8-y-old children.

Inadequate vitamin K intake has been associated with abnormal soft tissue calcification. Older adults may have insufficient intakes of vitamin K and respond less to vitamin K supplementation compared with younger adults. However, little is known about the determinants that influence the response to vitamin K supplementation. Our primary objective was to assess dietary and nondietary determinants of vitamin K status in healthy younger and older adults. In a nonrandomized, nonmasked study, 21 younger (18-40 y) and 21 older (55-80 y) men and women consumed a baseline diet (200 μg phylloquinone/d) for 5 d, a phylloquinone-restricted diet (10 μg phylloquinone/d) for 28 d, and a phylloquinone-supplemented diet (500 μg phylloquinone/d) for 28 d. Changes in vitamin K status markers in response to vitamin K depletion and repletion were studied and the influences of BMI, body fat, and circulating TG were assessed by including them as covariates in the model. Despite baseline differences in measures of vitamin K status, plasma phylloquinone tended to increase (P = 0.07) and the percentage of uncarboxylated osteocalcin and uncarboxylated prothrombin both improved with phylloquinone supplementation (P < 0.007), regardless of age group or sex. Only the excretion of urinary menadione, a vitamin K metabolite, was greater among younger adults in response to depletion than in older adults (P = 0.012), regardless of sex. Adiposity measures and circulating TG did not predict response of any measures. In conclusion, poor vitamin K status can be similarly improved with vitamin K supplementation, regardless of age group or sex.

Background: Cross-sectional data indicate that central adiposity is associated with cardiovascular disease risk, independent of total adiposity. The use of longitudinal data to investigate the relation between changes in fat distribution and the emergence of risk factors is limited., Objective: We tested the hypothesis that age-related change in waist circumference (to reflect central adiposity) during adolescence is a significant predictor of longitudinal change in cardiovascular disease risk, after adjustment for change in body mass index (BMI) z score (to reflect total adiposity) in a cohort of postmenarcheal adolescent females. We also tested whether race modified this relation., Design: We analyzed publicly available data from the National Heart, Lung, and Blood Institute Growth and Health Study. Longitudinal regression models were fitted to investigate the independent effects of changes in waist circumference on cardiovascular disease risk factors., Results: Steeper age-related increases in waist circumference over time were associated with a greater increase in LDL-cholesterol concentrations, systolic blood pressure, diastolic blood pressure, and homeostasis model assessment of insulin resistance, after adjustment for BMI z score, in white but not in black females. Change in waist circumference was not a statistically significant predictor of age-related changes in HDL-cholesterol, triglyceride, insulin, and glucose concentrations, after adjustment for changes in BMI z score, in either white or black females., Conclusions: Our research suggests that monitoring waist circumference in addition to BMI z score has the potential to identify adolescents at risk of the emergence of cardiovascular disease risk factors, at least in white females. The data also suggest that race may modify the relation between fat distribution pattern and cardiovascular disease risk factors.

Plasma lipoproteins and glucose homeostasis were evaluated after marked weight loss before and over 12 months following Roux-en-Y gastric-bypass (RYGBP) surgery in 19 morbidly obese women. Standard lipids, remnant-lipoprotein cholesterol (RLP-C); HDL-triglyceride (TG); apolipoproteins (apo) A-I, A-II, E, and A-I-containing HDL subpopulations; lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) mass and activity; plasma glucose and insulin levels were measured before and at 1, 3, 6, and 12 months after GBP surgery. Baseline concentrations of TG, RLP-C, glucose, and insulin were significantly higher in obese than in normal-weight, age-matched women, whereas HDL cholesterol (HDL-C), apoA-I, apoA-II, alpha-1 and alpha-2 levels were significantly lower. Over 1 year, significant decreases of body mass index, glucose, insulin, TG, RLP-C, HDL-TG, and prebeta-1 levels were observed with significant increases of HDL-C and alpha-1 levels (all P < 0.05). Changes of fat mass were correlated with those of LDL cholesterol (P = 0.018) and LCAT mass (P = 0.011), but not with CETP mass (P = 0.265). Changes of fasting plasma glucose concentrations were inversely correlated with those of CETP mass (P = 0.005) and alpha-1 level (P = 0.004). Changes of fasting plasma insulin concentrations were positively correlated with those of LCAT mass (P = 0.043) and inversely with changes of alpha-1 (P = 0.03) and alpha-2 (P = 0.05) concentrations. These results demonstrate beneficial changes in HDL remodeling following substantial weight loss induced by RYGBP surgery and that these changes are associated with improvement of glucose homeostasis in these patients.

Background: Vitamin E supplementation may be a potential strategy to prevent respiratory tract infections (RIs) in the elderly. The efficacy of vitamin E supplementation may depend on individual factors including specific single nucleotide polymorphisms (SNPs) at immunoregulatory genes., Objective: We examined whether the effect of vitamin E on RIs in the elderly was dependent on genetic backgrounds as indicated by SNPs at cytokine genes., Design: We used data and DNA from a previous vitamin E intervention study (200 IU vitamin E or a placebo daily for 1 y) in elderly nursing home residents to examine vitamin E-gene interactions for incidence of RI. We determined the genotypes of common SNPs at IL-1beta, IL-2, IL-6, IL-10, TNF-alpha, and IFN-gamma in 500 participants. We used negative binomial regression to analyze the association between genotype and incidence of infection., Results: The effect of vitamin E on lower RI depended on sex and the SNP at IL-10 -819G-->A (P = 0.03 for interaction for lower RI). Furthermore, we observed that subjects with the least prevalent genotypes at IL-2 -330A-->C (P = 0.02 for upper RI), IL-10 -819G-->A (P = 0.08 for upper RI), and IL-10 -1082C-->T (P < 0.001 for lower RI in men) had a lower incidence of RI independent of vitamin E supplementation., Conclusions: Studies that evaluate the effect of vitamin E on RIs should consider both genetic factors and sex because our results suggest that both may have a significant bearing on the efficacy of vitamin E. Furthermore, common SNPs at cytokine genes may contribute to the individual risk of RIs in the elderly. This trial was registered at clinicaltrials.gov as NCT00758914.

The accuracy of stated energy contents of reduced-energy restaurant foods and frozen meals purchased from supermarkets was evaluated. Measured energy values of 29 quick-serve and sit-down restaurant foods averaged 18% more than stated values, and measured energy values of 10 frozen meals purchased from supermarkets averaged 8% more than originally stated. These differences substantially exceeded laboratory measurement error but did not achieve statistical significance due to considerable variability in the degree of underreporting. Some individual restaurant items contained up to 200% of stated values and, in addition, free side dishes increased provided energy to an average of 245% of stated values for the entrees they accompanied. These findings suggest that stated energy contents of reduced-energy meals obtained from restaurants and supermarkets are not consistently accurate, and in this study averaged more than measured values, especially when free side dishes were taken into account. If widespread, this phenomenon could hamper efforts to self-monitor energy intake to control weight, and could also reduce the potential benefit of recent policy initiatives to disseminate information on food energy content at the point of purchase., (Copyright 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.)

Background: The skeletal protein osteocalcin is gamma-carboxylated by vitamin K. High serum uncarboxylated osteocalcin reflects low vitamin K status. In vitro and animal studies indicate that high uncarboxylated osteocalcin is associated with reduced insulin resistance. However, associations between osteocalcin and measures of insulin resistance in humans are less clear., Objective: Our aim was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin (total, uncarboxylated, and carboxylated) and insulin resistance in older men and women., Design: Cross-sectional associations between serum measures of total osteocalcin, carboxylated osteocalcin, and uncarboxylated osteocalcin and insulin resistance were examined in 348 nondiabetic men and women (mean age: 68 y; 58% female) by using the homeostasis model assessment of insulin resistance (HOMA-IR). Associations between each form of osteocalcin at baseline and 3-y change in HOMA-IR were examined in 162 adults (mean age: 69 y; 63% female) who did not receive vitamin K supplementation., Results: Lower circulating uncarboxylated osteocalcin was not associated with higher HOMA-IR at baseline or at 3-y follow-up. Those in the lowest tertiles of total osteocalcin and carboxylated osteocalcin at baseline had higher baseline HOMA-IR (P = 0.006 and P = 0.02, respectively). The concentration of carboxylated osteocalcin at baseline was inversely associated with a 3-y change in HOMA-IR (P = 0.002)., Conclusions: In older adults, circulating uncarboxylated osteocalcin was not associated with insulin resistance. In contrast, elevated carboxylated osteocalcin and total osteocalcin were associated with lower insulin resistance, which supports a potential link between skeletal physiology and insulin resistance in humans. The role of vitamin K status in this association remains unclear and merits further investigation. This trial is registered at clinicaltrials.gov as NCT00183001.

Background: Reduced rank regression (RRR) has been used to derive dietary pattern scores that predict linear combinations of disease biomarkers. The generalizability of these patterns to independent populations remains unknown., Objective: The goal was to examine the generalizability of dietary patterns from the following prior studies using RRR to predict type 2 diabetes mellitus (T2DM): the Nurses' Health Study (NHS), European Prospective Investigation into Cancer and Nutrition Germany (EPIC), and Whitehall II Study (WS)., Design: The relative weights of food groups of each dietary pattern were used to generate each dietary pattern score in the Framingham Offspring Study (n = 2879). Each of the external scores (confirmatory scores) was examined to determine whether it could predict incident T2DM during 7 y of follow-up as well as scores developed internally in the Framingham Offspring Study using a Cox-proportional hazard model adjusted for T2DM risk factors., Results: Intakes of meat products, refined grains, and soft drinks (caloric and noncaloric) were found to be common predictive components of all confirmatory scores, but fried foods, eggs, and alcoholic beverages were predictive in some, but not in all, confirmatory scores. On the basis of a continuous increase in the score by 1 SD, the NHS-based confirmatory score predicted T2DM risk (hazard ratio: 1.44; 95% CI: 1.25, 1.66). However, T2DM risk was only weakly predicted by the EPIC-based score (hazard ratio: 1.14; 95% CI: 0.99, 1.32) and the WS-based score (hazard ratio: 1.16; 95% CI: 1.00, 1.35)., Conclusions: The study suggested that dietary patterns that predict T2DM risk in different populations may not be generalizable to different populations. Additional dietary pattern studies should be conducted with regard to generalizability.

Background: A premise of the 2005 Dietary Guidelines for Americans (DGA) is chronic disease prevention., Objective: The goal was to determine whether a diet meeting the DGA is associated with less atherosclerotic lesion progression., Design: We used the data from 224 postmenopausal women with established coronary artery disease enrolled in the Estrogen Replacement and Atherosclerosis Study. Atherosclerosis progression was defined by repeated measures of quantitative angiography over a 3-y period. Adherence to the key DGA recommendations was measured by using the DGA Adherence Index (DGAI; possible range: 0-20), with each component weighted equally, and the modified DGAI score (wDGAI; possible range: -0.19-0.51), with each component weighted based on its relation to atherosclerosis progression. Mixed-model regression analyses were performed to assess the association between diet and atherosclerosis progression., Results: No women consumed a diet meeting all of the DGA recommendations. The mean (range) of the DGAI score was 14.1 (8.0-19.0). DGAI was not associated with atherosclerosis progression (P = 0.44), whereas wDGAI was inversely associated; a 1-SD difference in wDGAI was related to 0.049-mm less narrowing of the coronary arteries (SE = 0.017, P = 0.004)., Conclusions: In postmenopausal women with established heart disease, under the assumption that all DGA recommendations are similarly effective, overall adherence was not associated with atherosclerosis progression. However, assigning differential weights to the DGA recommendations, the adherence was significantly associated with slower atherosclerosis progression. Assuming equity of associations between all dietary recommendations and disease outcomes is a limitation in accurately examining the effectiveness of the DGA.

Background: Coronary artery calcification (CAC) is an independent predictor of cardiovascular disease. A preventive role for vitamin K in CAC progression has been proposed on the basis of the properties of matrix Gla protein (MGP) as a vitamin K-dependent calcification inhibitor., Objective: The objective was to determine the effect of phylloquinone (vitamin K1) supplementation on CAC progression in older men and women., Design: CAC was measured at baseline and after 3 y of follow-up in 388 healthy men and postmenopausal women; 200 received a multivitamin with 500 microg phylloquinone/d (treatment), and 188 received a multivitamin alone (control)., Results: In an intention-to-treat analysis, there was no difference in CAC progression between the phylloquinone group and the control group; the mean (+/-SEM) changes in Agatston scores were 27 +/- 6 and 37 +/- 7, respectively. In a subgroup analysis of participants who were > or =85% adherent to supplementation (n = 367), there was less CAC progression in the phylloquinone group than in the control group (P = 0.03). Of those with preexisting CAC (Agatston score > 10), those who received phylloquinone supplements had 6% less progression than did those who received the multivitamin alone (P = 0.04). Phylloquinone-associated decreases in CAC progression were independent of changes in serum MGP. MGP carboxylation status was not determined., Conclusions: Phylloquinone supplementation slows the progression of CAC in healthy older adults with preexisting CAC, independent of its effect on total MGP concentrations. Because our data are hypothesis-generating, further studies are warranted to clarify this mechanism. This trial was registered at clinicaltrials.gov as NCT00183001.

The proportion of the Latin American population above age 65 y is expected to rise substantially. To better define the prevalence of infectious diseases and micronutrient deficiencies, assess immunological status, and evaluate associations between nutritional status and infection, we performed a cross-sectional study of elderly Ecuadorians in a low-income peri-urban community in Quito, Ecuador. Culturally adapted questionnaires, delayed type hypersensitivity (DTH) skin response, micronutrient, and immunological assays were performed in randomly selected Ecuadorians aged > or = 65 y. Multiple linear and logistic regression models were developed to assess relationships between micronutrient concentrations and history of infection, DTH, and immune function. Participants (n = 352; mean age +/- SD, 74.4 +/- 6.4 y) recalled recent episodes of colds/influenza-like syndromes (62.8%), cough (61.0%), urinary tract infection (37.9%), diarrhea (32.2%), fever (24.1%), and pneumonia (3.5%). A prospective substudy of respiratory infections (RI) in 203 elderly revealed similar findings. Colds and pneumonia occurred in 42.8 and 7.9% of participants, respectively, during 737 person-weeks of observation (3.6 +/- 1.1 wk per person). Anemia and micronutrient deficiencies, especially for vitamins C, D, B-6, and B-12 and folic acid and zinc, were common. Plasma vitamin C was associated with interferon-gamma (IFNgamma) (P < 0.01) and zinc with IFNgamma and interleukin-2 (each P < 0.0001). RI history was associated with any micronutrient deficiency (P < 0.001). The burden of infectious diseases, micronutrient deficiencies, and anemia was substantial in this elderly Ecuadorian population. Deficiencies of essential vitamins and minerals place these elderly adults at risk for infections through their negative impact on immune function.

Background: Vitamin K modulates cytokines involved in bone turnover, including interleukin-6 (IL-6) and osteoprotegerin in vitro., Objective: The objective of this study was to assess 1) associations between measures of vitamin K status [plasma phylloquinone and serum percentage of undercarboxylated osteocalcin (%ucOC)] and IL-6, osteoprotegerin, and C-reactive protein (CRP) concentrations and 2) the effect of daily 500 mug phylloquinone supplementation for 3 y on cytokine concentrations., Design: Concentrations of IL-6, osteoprotegerin, and CRP and bone mineral density (BMD) were measured at baseline and after 3 y of follow-up in 379 healthy men and women (60-81 y; 58.5% women) participating in a randomized trial that studied the effect of vitamin K supplementation on bone loss., Results: Cross-sectionally, plasma phylloquinone was inversely associated with IL-6 and CRP, whereas serum %ucOC was inversely associated with IL-6. Osteoprotegerin was associated positively with plasma phylloquinone and inversely with %ucOC. No differences were observed in the 3-y change in IL-6, osteoprotegerin, and CRP concentrations between participants who received phylloquinone supplementation and those who did not. Overall, no association was observed between the 3-y changes in circulating cytokines and BMD., Conclusions: Poor vitamin K status was associated with high concentrations of cytokines involved in bone turnover, but vitamin K supplementation did not confer a decrease in cytokine concentrations. The healthy status of this cohort may explain a lack of effect of vitamin K supplementation on cytokine concentrations. This trial was registered with www.clinicaltrials.gov as NCT00183001.

Background: Zinc plays an important role in immune function. The association between serum zinc and pneumonia in the elderly has not been studied., Objective: The objective was to determine whether serum zinc concentrations in nursing home elderly are associated with the incidence and duration of pneumonia, total and duration of antibiotic use, and pneumonia-associated and all-cause mortality., Design: This observational study was conducted in residents from 33 nursing homes in Boston, MA, who participated in a 1-y randomized, double-blind, and placebo-controlled vitamin E supplementation trial; all were given daily doses of 50% of the recommended dietary allowance of essential vitamins and minerals, including zinc. Participants with baseline (n = 578) or final (n = 420) serum zinc concentrations were categorized as having low (<70 microg/dL) or normal (>or=70 microg/dL) serum zinc concentrations. Outcome measures included the incidence and number of days with pneumonia, number of new antibiotic prescriptions, days of antibiotic use, death due to pneumonia, and all-cause mortality., Results: Compared with subjects with low zinc concentrations, subjects with normal final serum zinc concentrations had a lower incidence of pneumonia, fewer (by almost 50%) new antibiotic prescriptions, a shorter duration of pneumonia, and fewer days of antibiotic use (3.9 d compared with 2.6 d) (P

Background: There remains no consensus about the optimal dietary composition for sustained weight loss., Objective: The objective was to examine the effects of 2 dietary macronutrient patterns with different glycemic loads on adherence to a prescribed regimen of calorie restriction (CR), weight and fat loss, and related variables., Design: A randomized controlled trial (RCT) of diets with a high glycemic load (HG) or a low glycemic load (LG) at 30% CR was conducted in 34 healthy overweight adults with a mean (+/-SD) age of 35 +/- 6 y and body mass index (kg/m(2)) of 27.6 +/- 1.4. All food was provided for 6 mo in diets controlled for confounding variables, and subjects self-administered the plans for 6 additional months. Primary and secondary outcomes included energy intake measured by doubly labeled water, body weight and fatness, hunger, satiety, and resting metabolic rate., Results: All groups consumed significantly less energy during CR than at baseline (P < 0.01), but changes in energy intake, body weight, body fat, and resting metabolic rate did not differ significantly between groups. Both groups ate more energy than provided (eg, 21% and 28% CR at 3 mo and 16% and 17% CR at 6 mo with HG and LG, respectively). Percentage weight change at 12 mo was -8.04 +/- 4.1% in the HG group and -7.81 +/- 5.0% in the LG group. There was no effect of dietary composition on changes in hunger, satiety, or satisfaction with the amount and type of provided food during CR., Conclusions: These findings provide more detailed evidence to suggest that diets differing substantially in glycemic load induce comparable long-term weight loss.

Background: Smoking causes genetic damage in buccal cells and increases the risk of oral cancer. Because folate is instrumental in DNA synthesis and repair, it is a determinant of genetic stability and therefore might attenuate the genotoxic effects of smoking., Objective: Our aim was to compare the presence of folate metabolites and select indicators of genetic damage in the mouths of chronic smokers and nonsmokers., Design: Dietary, biochemical, and molecular correlates of folate status were measured in healthy smoker (n = 35) and nonsmoker (n = 21) groups of comparable age, sex, and body mass indexes., Results: After correction for dietary intake, the smokers displayed lower plasma, erythrocyte, and buccal mucosal cell (BMC) folate (20%, 32%, and 50% lower, respectively; P < 0.05) and lower plasma vitamin B-12 and pyridoxal 5-phosphate (P < 0.05) than did nonsmokers. Folate in the BMCs of smokers comprised significantly greater proportions of pteroylmonoglutamate, formyltetrahydrofolate, and 5,10-methenyltetrahyrofolate than did folate in the BMCs of nonsmokers. Although the degree of genomic methylation and uracil incorporation in the buccal cells of the 2 groups were not significantly different, the BMC micronucleus index, a cytologic indicator of genetic damage, in the smokers was 2-fold that of the nonsmokers (9.57 compared with 4.44 micronuclei/1000 cells; P < 0.0001). Neither systemic nor oral folate status was an independent predictor of micronuclei., Conclusions: Chronic smoking is associated with a lower systemic status of several B vitamins, reduced oral folate, and changes in folate form distribution in the mouth. However, the cytologic damage that is evident in the mouths of smokers does not correlate with oral folate status.

Our objective was to evaluate the associations of individual apolipoprotein A-I (apoA-I)-containing HDL subpopulation levels with ABCA1- and scavenger receptor class B type I (SR-BI)-mediated cellular cholesterol efflux. HDL subpopulations were measured by nondenaturing two-dimensional gel electrophoresis from 105 male subjects selected with various levels of apoA-I in pre-beta-1, alpha-1, and alpha-3 HDL particles. ApoB-containing lipoprotein-depleted serum was incubated with [(3)H]cholesterol-labeled cells to measure efflux. The difference in efflux between control and ABCA1-upregulated J774 macrophages was taken as a measure of ABCA1-mediated efflux. SR-BI-mediated efflux was determined using cholesterol-labeled Fu5AH hepatoma cells. Fractional efflux values obtained from these two cell systems were correlated with the levels of individual HDL subpopulations. A multivariate analysis showed that two HDL subspecies correlated significantly with ABCA1-mediated efflux: small, lipid-poor pre-beta-1 particles (P=0.0022) and intermediate-sized alpha-2 particles (P=0.0477). With regard to SR-BI-mediated efflux, multivariate analysis revealed significant correlations with alpha-2 (P=0.0004), alpha-1 (P=0.0030), pre-beta-1 (P=0.0056), and alpha-3 (P=0.0127) HDL particles. These data demonstrate that the small, lipid-poor pre-beta-1 HDL has the strongest association with ABCA1-mediated cholesterol even in the presence of all other HDL subpopulations. Cholesterol efflux via the SR-BI pathway is associated with several HDL subpopulations with different apolipoprotein composition, lipid content, and size.

Background: Longitudinal data on energy expenditure in children and adolescents are scarce., Objective: The purpose of this study was to examine changes in energy expenditure and physical activity in girls from late childhood through midadolescence., Design: We measured total energy expenditure (TEE) by doubly labeled water, resting metabolic rate (RMR) by indirect calorimetry, body composition by 18O dilution, and time spent in activity by an activity diary in 28 initially nonobese girls at approximately 10, approximately 12, and approximately 15 y of age. Changes with age in TEE, RMR, and activity energy expenditure (AEE), both in absolute terms and in adjusted analyses, and in physical activity level (PAL) and time spent sleeping, being sedentary, and in moderate and vigorous activity were evaluated by mixed-model repeated-measures analyses., Results: Absolute TEE and AEE increased significantly from age 10 to age 15 y (P < 0.0001 for both). Absolute RMR at ages 12 and 15 y did not differ significantly, despite significant increases in fat-free mass and fat mass between the visits. PAL was significantly higher (P < 0.0001) at age 15 y than at age 10 or 12 y, whereas time spent being sedentary increased significantly from age 10 to age 15 y (P < 0.001), and AEE adjusted for fat-free mass appeared to decrease over the same interval., Conclusion: Conclusions drawn regarding changes with age in physical activity depend on the measure of physical activity assessed.

Background: Cases of enhanced anticoagulant effect in response to high-dose vitamin E supplementation have been reported among patients taking oral anticoagulants. Although a vitamin E-vitamin K interaction was proposed to underlie this effect, it has not been systematically investigated in adults with normal baseline coagulation status., Objective: The objective was to study the effect of 12 wk of supplementation with 1000 IU RRR-alpha-tocopherol/d on biochemical measures of vitamin K status in men and women not taking oral anticoagulants., Design: Vitamin K status, which was assessed with the use of plasma phylloquinone concentrations, the degree of under-gamma-carboxylation of prothrombin (proteins induced by vitamin K absence-factor II, PIVKA-II), and the percentage of undercarboxylated osteocalcin (ucOC), was determined in 38 men and women with rheumatoid arthritis (study A) and in 32 healthy men (study B) participating in 2 independent, 12-wk randomized clinical trials of vitamin E supplementation (1000 IU/d)., Results: Mean (+/- SD) PIVKA-II increased from 1.7 +/- 1.7 to 11.9 +/- 16.1 ng/mL (P < 0.001) in study A and from 1.8 +/- 0.6 to 5.3 +/- 3.9 ng/mL (P < 0.001) in study B in response to 12 wk of vitamin E supplementation. An increase in PIVKA-II is indicative of poor vitamin K status. In contrast, the other measures of vitamin K status (ie, plasma phylloquinone concentration and percentage of ucOC) did not change significantly in response to the supplementation., Conclusions: High-dose vitamin E supplementation increased PIVKA-II in adults not receiving oral anticoagulant therapy. The clinical significance of these changes warrants further investigation, but high doses of vitamin E may antagonize vitamin K. Whether such an interaction is potentially beneficial or harmful remains to be determined.

Background: High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease, stroke, and dementia and are relatively common in older adults., Objective: We assessed the effect of breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 on vitamin and homocysteine status., Design: A randomized, double-blind trial was conducted in 189 volunteers aged 50-85 y. The subjects had no history of hypertension, anemia, asthma, cancer, or cardiovascular or digestive disease and did not regularly consume multiple or B vitamin supplements or highly fortified breakfast cereal. Subjects were randomly assigned to consume 1 cup (0.24 L) breakfast cereal fortified with 440 microg folic acid, 1.8 mg vitamin B-6, and 4.8 microg vitamin B-12 or placebo cereal for 12 wk. Blood was drawn at 0, 2, 12, and 14 wk. Methionine-loading tests were conducted at baseline and week 14., Results: Final baseline-adjusted plasma homocysteine concentrations were significantly lower and B vitamin concentrations were significantly higher in the treatment group than in the placebo group (P < 0.001). The percentage of subjects with plasma folate concentrations < 11 nmol/L decreased from 2% to 0%, with vitamin B-12 concentrations < 185 pmol/L from 9% to 3%, with vitamin B-6 concentrations < 20 nmol/L from 6% to 2%, and with homocysteine concentrations > 10.4 micromol/L (women) or > 11.4 micromol/L (men) from 6.4% to 1.6%. The percentage of control subjects with values beyond these cutoff points remained nearly constant or increased., Conclusions: In this relatively healthy group of volunteers, consumption of 1 cup fortified breakfast cereal daily significantly increased B vitamin and decreased homocysteine concentrations, including post-methionine-load homocysteine concentrations.

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: Little is known about the determinants of individual variability in body weight and fat loss after gastric bypass surgery or about the effects of massive weight loss induced by this surgery on energy requirements., Objectives: The objectives were to determine changes in energy expenditure and body composition with weight loss induced by gastric bypass surgery and to identify presurgery predictors of weight loss., Design: Thirty extremely obese women and men with a mean (+/- SD) age of 39.0 +/- 9.6 y and a body mass index (BMI; in kg/m(2)) of 50.1 +/- 9.3 were tested longitudinally under weight-stable conditions before surgery and after weight loss and stabilization (14 +/- 2 mo). Total energy expenditure (TEE), resting energy expenditure (REE), body composition, and fasting leptin were measured., Results: Subjects lost 53.2 +/- 22.2 kg body weight and had significant decreases in REE (-2.4 +/- 1.0 MJ/d; P < 0.001) and TEE (-3.6 +/- 2.5 MJ/d; P < 0.001). Changes in REE were predicted by changes in fat-free mass and fat mass. The average physical activity level (TEE/REE) was 1.61 at both baseline and follow-up (P = 0.98). Weight loss was predicted by baseline fat mass and BMI but not by any energy expenditure variable or leptin. Measured REE at follow-up was not significantly different from predicted REE., Conclusions: TEE and REE decreased by 25% on average after massive weight loss induced by gastric bypass surgery. REE changes were predicted by loss of body tissue; thus, there was no significant long-term change in energy efficiency that would independently promote weight regain.

Background: The conventional deuterated-retinol-dilution (DRD) technique provides a quantitative estimate of total body stores of vitamin A in humans. The procedure requires equilibration of serum deuterated retinol with nondeuterated retinol after administration of an oral dose of deuterated vitamin A. Equilibration takes approximately 3 wk to complete., Objective: Our goal was to develop a predictive mathematical formula for quantitative assessment of total body stores of vitamin A in adults by using a procedure that takes less time to perform because serum isotope equilibration is not required, so that blood drawing can be done 3 d, instead of approximately 3 wk, after isotope dosing., Design: Ratios of serum deuterated to nondeuterated retinol (D:H retinol) were determined in Filipino adults (n = 68) 3 and 20 d after an oral dose of 0.015 mmol [(2)H(4)]retinyl acetate and in Guatemalan adults (n = 15) 3 and 21 d after a 0.030-mmol dose. D:H retinol values 20 or 21 d after the isotope dose were used in a mathematical formula to obtain quantitative estimates of total body stores of vitamin A that were then correlated with serum D:H retinol values 3 d after the isotope dose., Results: The relation between these variables was nonlinear and was described by the following equation: total body stores of vitamin A (in mmol retinol) = 0.00468 x 10(37(isotope dose in mmol))/D:H retinol in serum 3 d after the isotope dose., Conclusion: A 3-d DRD technique could be used for quantitative assessment of total body stores of vitamin A; this technique takes less time than does the conventional DRD technique.

Background: High body iron stores may increase the risk of several chronic diseases. Whether dietary factors contribute to the risk of high iron stores is unknown., Objective: We assessed the relation between dietary factors and the risk of high iron stores in the elderly Framingham Heart Study cohort., Design: We examined the relation between the usual intake of dietary factors (food-frequency questionnaire) and the risk of high iron stores (serum ferritin >300 and 200 micro g/L in men and women, respectively) in 614 subjects aged 68-93 y., Results: The risk of high iron stores was significantly higher 1) in subjects who took > or =30 mg supplemental Fe/d than in nonusers [odds ratio (OR): 4.32; 95% CI: 1.63, 11.47], 2) in subjects who consumed >21 servings of fruit/wk than in those who consumed < or =14 servings/wk (OR: 2.88; 95% CI: 1.26, 6.61), and 3) in subjects who consumed >4 but <7 or > or=7 servings of red meat/wk than in those who consumed < or =4 servings/wk (ORs: 2.94 and 3.61, respectively; 95% CIs: 1.33, 6.47 and 1.57, 8.27, respectively). Whole-grain intake (>7 servings/wk) was inversely associated (OR: 0.23; 95% CI: 0.07, 0.75)., Conclusions: Among elders, intakes of highly bioavailable forms of iron (supplemental iron and red meat) and of fruit, a dietary source of an enhancer of nonheme-iron absorption (vitamin C), promote high iron stores, whereas foods containing phytate (whole grains) decrease these stores. Individual dietary patterns may be important modulators of high iron stores.

Studies that have compared the absorption of phylloquinone from green vegetables and oils have equivocal results. To address differences in approaches used to assess absorption of phylloquinone, a 24-h absorption study was conducted in 18 younger (20-40 y) and 18 older (60-80 y) men and women as part of a larger metabolic study that compared changes in vitamin K status in response to broccoli and phylloquinone-fortified oil (377 +/- 46 and 417 +/- 45 micro g/d, respectively). Absorption was defined as the 24-h area under the curve (AUC) for plasma phylloquinone concentrations (both unadjusted and adjusted for triglyceride concentrations). The mean AUC for plasma phylloquinone concentrations (both unadjusted and adjusted) were significantly greater after consumption of the phylloquinone-fortified oil diet compared with the broccoli diet (P < 0.001). However, there were no differences between the two treatments in 24-h fasting plasma phylloquinone concentrations. Although there were no age differences in the AUC for plasma phylloquinone adjusted for triglycerides, older adults had significantly higher plasma phylloquinone concentrations (both unadjusted and adjusted) at 0 and 24 h than the younger adults (P < 0.001). These data emphasize that the use of different approaches for the assessment of vitamin K absorption can result in disparate conclusions.