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Dietary polyphenols have been shown to have a beneficial impact on blood pressure. To investigate the effect of daily consumption of a low calorie cranberry juice beverage (a rich source of polyphenols) on blood pressure of healthy adults (n=56), we conducted a parallel arm, double-blind, randomized, placebo-controlled trial. Volunteers were men (n=26) and women (n=30), aged 51+11 years, with a body weight of 79.3+8.8 kg and BMI of 28.4+4.3 (mean+SD). Treatments were a low calorie cranberry juice beverage or a color/flavor/calorie-matched placebo beverage, both of which were incorporated into a controlled diet for 8 weeks. During the controlled diet, volunteers consumed a base diet, consisting of typical American foods, scaled to meet their individual energy requirement such that body weight did not change during the study. Blood pressure was measured by a standardized protocol at the beginning of the intervention, after 4 weeks of treatment, and after 8 weeks of treatment. Systolic and diastolic blood pressure values for placebo and cranberry juice treatments at 4 weeks and 8 weeks were compared with a mixed model ANOVA. Blood pressure measures at 4 and 8 weeks of treatment for placebo and cranberry juice were also compared to baseline using a repeated measures ANOVA. After 8 weeks, diastolic blood pressure was significantly lower for the cranberry juice group compared to the placebo group (LSmeans + SEM of 72.2+1.1 mm Hg for placebo vs. 68.6+1.1 mm Hg for cranberry juice, respectively, p=0.029). When 8 week blood pressure values were compared to baseline, cranberry juice was associated with a significant decrease in diastolic BP (73.9+1.6 mm Hg at baseline vs. 70.9+1.6 mm Hg at 8 wk, p=0.049) and a trend toward decreased systolic BP (121.9+3.2 mm Hg at baseline vs. 118.6+3.1 mm Hg at 8 wk, p=0.12), while the placebo was associated with no change from baseline (systolic of 111.5+2.4 mm Hg at baseline vs. 112.3+2.2 mm Hg at 8 wk, p=0.89; diastolic of 68.1+1.5 mm Hg at baseline vs. 68.6+1.5 mm Hg at 8 wk, p=0.37). In conclusion, incorporation of a low calorie cranberry juice beverage into the diet of healthy adults appears to result in improvements in blood pressure.

Flavanols may provide protection against insulin resistance, but little is known about the amounts and types of flavanols that may be efficacious.This study was designed to determine whether cocoa flavanols, over a range of intakes, improve biomarkers of glucose regulation, inflammation and hemostasis in obese adults at risk for insulin resistance. As an adjunct, green tea and cocoa flavanols were compared for their ability to modulate these biomarkers. In a randomized crossover design, 20 adults consumed a controlled diet for 5 days along with four cocoa beverages containing 30-900 mg flavanol per day, or tea matched to a cocoa beverage for monomeric flavanol content.Cocoa beverages produced no significant changes in glucose, insulin, total area under the concentration-time curve (AUC) for glucose or total insulin AUC. As the dose of cocoa flavanols increased, total 8-isoprostane concentrations were lowered (linear contrast, P=0.02), as were C-reactive protein (CRP) concentrations (linear contrast, P=0.01). The relationship between cocoa flavanol levels and interleukin-6 (IL-6) concentrations was quadratic, suggesting that a maximum effective dose was achieved (quadratic contrast, P=0.01). There were no significant effects on measured indices of glucose regulation, nor on those of total 8-isoprostane, CRP and IL-6 concentrations, when cocoa and green tea were compared. However, relative to cocoa, green tea lowered fibrinogen concentrations (P=0.0003).Short-term intake of cocoa and green tea flavanols does not appear to improve glucose metabolism; they do affect selected markers of one or more measures of oxidative stress, inflammation or hemostasis in obese adults at risk for insulin resistance.

Using linear regression models, we studied the main and 2-way interaction effects of the predictor variables gender, age, BMI, and 64 folate/vitamin B-12/homocysteine (Hcy)/lipid/cholesterol-related single nucleotide polymorphisms (SNP) on log-transformed plasma Hcy normalized by RBC folate measurements (nHcy) in 373 healthy Caucasian adults (50% women). Variable selection was conducted by stepwise Akaike information criterion or least angle regression and both methods led to the same final model. Significant predictors (where P values were adjusted for false discovery rate) included type of blood sample [whole blood (WB) vs. plasma-depleted WB; P < 0.001] used for folate analysis, gender (P < 0.001), and SNP in genes SPTLC1 (rs11790991; P = 0.040), CRBP2 (rs2118981; P < 0.001), BHMT (rs3733890; P = 0.019), and CETP (rs5882; P = 0.017). Significant 2-way interaction effects included gender × MTHFR (rs1801131; P = 0.012), gender × CRBP2 (rs2118981; P = 0.011), and gender × SCARB1 (rs83882; P = 0.003). The relation of nHcy concentrations with the significant SNP (SPTLC1, BHMT, CETP, CRBP2, MTHFR, and SCARB1) is of interest, especially because we surveyed the main and interaction effects in healthy adults, but it is an important area for future study. As discussed, understanding Hcy and genetic regulation is important, because Hcy may be related to inflammation, obesity, cardiovascular disease, and diabetes mellitus. We conclude that gender and SNP significantly affect nHcy.

There are 2 predominant sources of dietary trans fatty acids (TFA) in the food supply, those formed during the industrial partial hydrogenation of vegetable oils (iTFA) and those formed by biohydrogenation in ruminants (rTFA), including vaccenic acid (VA) and the naturally occurring isomer of conjugated linoleic acid, cis-9, trans-11 CLA (c9,t11-CLA). The objective of this review is to evaluate the evidence base from epidemiological and clinical studies to determine whether intake of rTFA isomers, specifically VA and c9,t11-CLA, differentially affects risk of cardiovascular disease (CVD) and cancer compared with iTFA. In addition, animal and cell culture studies are reviewed to explore potential pro- and antiatherogenic mechanisms of VA and c9,t11-CLA. Some epidemiological studies suggest that a positive association with coronary heart disease risk exists between only iTFA isomers and not rTFA isomers. Small clinical studies have been conducted to establish cause-and-effect relationships between these different sources of TFA and biomarkers or risk factors of CVD with inconclusive results. The lack of detection of treatment effects reported in some studies may be due to insufficient statistical power. Many studies have used doses of rTFA that are not realistically attainable via diet; thus, further clinical studies are warranted. Associations between iTFA intake and cancer have been inconsistent, and associations between rTFA intake and cancer have not been well studied. Clinical studies have not been conducted investigating the cause-and-effect relationship between iTFA and rTFA intake and risk for cancers. Further research is needed to determine the health effects of VA and c9,t11-CLA in humans.

Background: Whereas the negative effect of consuming trans fatty acids found in partially hydrogenated vegetable oils on cardiovascular disease (CVD) risk is well established, the effect of trans fatty acids from ruminant sources (rTFAs) on CVD risk factors has not yet been established, particularly among women. Objective: We investigated the effects of a butter naturally enriched in rTFAs, of which vaccenic acid is the predominant isomer, on plasma lipid concentrations among healthy women. Design: In a double-blind, randomized, crossover controlled study, 61 healthy women aged 19–70 y were fed 2 isoenergetic diets lasting 4 wk each. The 2 diets were defined as moderately high in rTFAs (3.7 g/d, 1.5% of daily energy) and control (0.9 g/d, 0.3% of daily energy). Results: No significant effect of the rTFA diet was found on total plasma cholesterol, LDL cholesterol, apolipoprotein B, apolipoprotein A-I, and triglyceride concentrations compared with the control diet. There was a small yet statistically significant reduction in plasma HDL-cholesterol concentrations with the rTFA diet (−2.8%; P = 0.004), which was significant (P for the BMI × treatment interaction = 0.006) among women with a BMI (in kg/m2) ≥25 (−5.2%; P = 0.004; n = 18) but not among women with a BMI

The paper by Preis et al. (1) contains potentially misleading statements concerning the impact of within-person biomarker variation on the Observing Protein and Energy Nutrition (OPEN) Study results. The major theme of the paper is estimation of deattenuation factors and correlations between intakes reported on a food frequency questionnaire or 24-hour diet recall and true usual intake. A second theme is estimating correlations between person-specific systematic errors in the food frequency questionnaire and 24-hour diet recall. Two models, labeled “(1)” in the paper and another, unlabeled, that we refer to as “model 2,” are considered. Model 1 assumes that 24-hour diet recalls provide unbiased measures of usual intake, whereas the biomarkers are biased. Model 2 assumes the reverse. We see no reason to consider model 1 for the cases of doubly labeled water and urinary nitrogen. Previous feeding studies with urinary nitrogen (2–4) and indirect calorimetry studies with doubly labeled water (3, 5–7) have found no appreciable bias in these recovery biomarkers (8). Although model 1 has been previously used (8, 9), it was only in studies with concentration biomarkers known to be biased. Claiming that doubly labeled water within-person variation is underestimated in the OPEN Study, Preis et al. (1) use an alternative estimate from the Automated Multiple-Pass Method (AMPM) Validation Study to reanalyze the OPEN Study’s deattenuation factors in their Table 5. However, as shown in the Appendix (1), the deattenuation factor does not depend on biomarker within-person variation under model 2. As a result, the authors’ estimated deattenuation factors for the OPEN Study food frequency questionnaire under model 2 (0.07 for energy, 0.16 for protein, and 0.33 for protein density) are similar to those reported by Kipnis et al. (10) (0.080 and 0.039 for energy, 0.156 and 0.137 for protein, and 0.404 and 0.316 for protein density (men and women, respectively)). Small differences are probably due to minor analytical differences from Kipnis et al. (10) (use of the second vs. the first food frequency questionnaire and the combining of analyses for men and women). We agree that the level of biomarker within-person variation does affect correlations between self-report and true usual intake and also that the estimated within-person variation could be sensitive to time between repeats. However, we see little evidence that this affected the OPEN Study results. The correlations for the OPEN Study reported in Table 4 (using the AMPM Validation Study within-person variation) were 0.25 for energy, 0.30 for protein, and 0.36 for protein density. Kipnis et al. (10) reported 0.199 and 0.098 for energy (men and women), 0.323 and 0.298 for protein, and 0.431 and 0.356 for protein density. The energy estimates of Kipnis et al. are slightly lower than the authors’ estimate of 0.25. However, epidemiologic analyses rarely include energy alone. Therefore, protein density is more relevant, and the larger AMPM Validation Study doubly labeled water within-person variance appears to have negligible impact on the protein density correlation. Thus, the results do not support the conclusion that the 2-week period between doubly labeled water repeats in the OPEN Study led to “underestimation of the FFQ’s [food frequency questionnaire’s] validity” (1, p. 684). Finally, Preis et al. (1) suggest in their Figure 1 that the short period between doubly labeled water repeats exaggerated the correlation between food frequency questionnaire and 24-hour diet recall systematic errors. Recalculation using the AMPM Validation Study biomarker within-person variation gave correlations of 0.31 for energy, 0.25 for protein, and 0.59 for protein density. Kipnis et al. (10) reported 0.45 and 0.28 for energy (men and women), 0.18 and 0.24 for protein, and 0.40 and 0.94 for protein density. Averaging over men and women gives values of 0.365, 0.21, and 0.67—not materially different from those reported by Preis et al. Although the timing of repeated biomarker measurements in a validation study deserves careful consideration, we think Preis et al. greatly exaggerated its potential impact with regard to previously reported estimates from the OPEN Study.

Low overnight urinary melatonin metabolite concentrations have been associated with increased risk for breast cancer among postmenopausal women. The Postmenopausal Women's Alcohol Study was a controlled feeding study to test the effects of low to moderate alcohol intake on potential risk factors for breast cancer including serum and urinary levels of hormones and other biomarkers. Previously, we observed significant increases in concentrations of serum estrone sulfate and dehydroepiandrosterone sulfate in participants after consumption of 15 or 30 g (one or two drinks) of alcohol per day.In the present analysis, we evaluated the relationship of alcohol consumption with 24-h urinary 6-sulfatoxymelatonin (6-SMT) concentration (micrograms per 24 h).Healthy postmenopausal women (n = 51) consumed a controlled diet plus each of three treatments (a nonalcoholic placebo beverage or 15 or 30 g alcohol/d) during three 8-wk periods in random order under conditions of weight maintenance.6-SMT was measured in 24-h urine samples that were collected at entry into the study (baseline) and at the midpoint (4 wk) and end (8 wk) of each of the three diet periods.Concentration of 6-SMT was not significantly modified by the alcohol treatment after adjustment for body mass index, hours of sleep, daylight hours, and baseline level of 6-SMT.These results suggest that low to moderate daily alcohol consumption does not significantly affect 24-h urinary levels of melatonin among healthy postmenopausal women.

Background Intermittent fasting (IF) improves healthy lifespan in animals by a mechanism involving reduced oxidative damage and increased resistance to stress. However, no studies have evaluated the impact of controlled meal frequency on immune responses in human subjects. Objective A study was conducted to establish the effects of controlled diets with different meal frequencies, but similar daily energy intakes, on cytokine production in healthy male and female subjects. Design In a crossover study design with an intervening washout period, healthy normal weight middle-age male and female subjects (n = 15) were maintained for 2 months on controlled on-site one meal per day (OMD) or three meals per day (TMD) isocaloric diets. Serum samples and peripheral blood mononuclear cells (PBMCs) culture supernatants from subjects were analyzed for the presence of inflammatory markers using a multiplex assay. Results There were no significant differences in the inflammatory markers in the serum of subjects on the OMD or TMD diets. There was an increase in the capacity of PBMCs to produce cytokines in subjects during the first month on the OMD or TMD diets. Lower levels of TNF-α, IL-17, MCP-1 and MIP-1β were produced by PBMCs from subjects on the OMD versus TMD diet. Conclusions PBMCs of subjects on controlled diets exhibit hypersensitivities to cellular stimulation suggesting that stress associated with altered eating behavior might affect cytokine production by immune cells upon stimulation. Moreover, stimulated PBMCs derived from healthy individuals on a reduced meal frequency diet respond with a reduced capability to produce cytokines.

Measurement of body composition in vivo is important in many nutritional studies. One method for estimating body composition is total body electrical conductance (TOBEC). The TOBEC methodology is based on measuring changes of an electromagnetic field that are proportional to lean body mass (LBM). Sprague-Dawley rats (n = 117) ranging in age from 49 to 105 days were measured by TOBEC, and the TOBEC results were compared with direct carcass chemical analyses. The rats ranged in weight from 155 to 500 g. Mean LBM was 92.4% of total body weight (b.wt.), and mean body fat was 7.4% of total b.wt. Mean hydration of LBM was 71.7% and decreased (r = -0.59, p0.0001) with age. Using the manufacturer's supplied equation, TOBEC measurement underestimated actual LBM by 12% (p0.0001). As a consequence of this error, a new prediction equation was generated using half of the data set, and this equation was cross-validated with the other half of the data set. The mean LBM calculated from the new prediction equation was not different from chemically determined LBM, but the estimated percent body fat of some rats was negative. Thus, TOBEC may be useful in predicting mean LBM of a population, but this indirect method may lack the sensitivity to provide accurate estimates of body composition of an individual.

International audience; Substantial evidence clearly demonstrates the deleterious effects of industrially-produced trans fatty acids (TFA); however, data are lacking from large, well controlled human feeding studies that directly compare the effects of industrially-produced and naturally-occurring TFA. The purpose of the current study is to determine whether consumption of TFA derived from different sources differentially affect risk factors of cardiovascular disease (CVD). The study was a randomized, crossover design, controlled-feeding intervention designed to compare the effects of the following diet treatments on risk factors of CVD: low TFA diet (base diet, 34% energy from fat; 0.1% energy from TFA), base diet with vaccenic acid (3.0% energy), base diet with mixed isomers of TFA from partially hydrogenated vegetable oil (3.0% energy), and base diet with cis-9, trans-11 CLA (1.0% energy). The added energy from TFA replaced energy from stearic acid. Participants were required to be between the ages of 25 and 65 years, have a body mass index between 20 and 38 kg/m(2), total cholesterol

We studied the interrelationship of diet and plant sterols (PS) on plasma lipids, lipoproteins and carotenoids. Mildly hypercholesterolemic men (n = 13) and postmenopausal women (n = 9) underwent four randomized, crossover, double-blind, controlled feeding periods of 23 days each. The design consisted of two levels of PS (0 and 3.3 g/day) and two background diets having fat content either typical of the American diet (total and saturated fat at 33.5 and 13.2% of energy, respectively), or a Step 1 type of diet (total and saturated fat at 26.4 and 7.7% of energy, respectively). Plasma total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, Apo A1 and Apo B were 4.3, 5.3, 4.5, 2.8 and 2.5% lower, respectively (P ≤ 0.0001

Background: The US Department of Agriculture Automated Multiple-Pass Method (AMPM) is used for collecting 24-h dietary recallsinWhatWeEatInAmerica,thedietaryinterviewcomponent of the National Health and Nutrition Examination Survey. Because thedatahaveimportantprogramandpolicyapplications,itisessential that the validity of the method be tested. Objective:TheaccuracyoftheAMPMwasevaluatedbycomparing reported energy intake (EI) with total energy expenditure (TEE) by using the doubly labeled water (DLW) technique. Design:The 524 volunteers, aged 30–69 y, included an equal number of men and women recruited from the Washington, DC, area. EachsubjectwasdosedwithDLWonthefirstdayofthe2-wkstudy period; three 24-h recalls were collected during the 2-wk period by using the AMPM. The first recall was conducted in person, and subsequent recalls were over the telephone. Results: Overall, the subjects underreported EI by 11% compared with TEE. Normal-weight subjects [body mass index (in kg/m 2 ) 25] underreported EI by 3%. By using a linear mixed model, 95% CIs were determined for the ratio of EI to TEE. Approximately 78% of men and 74% of women were classified as acceptable energy reporters (within 95% CI of EI:TEE). Both the percentage by which energy was underreported and the percentage of subjects classified as low energy reporters (95% CI of EI:TEE) were highest for subjects classified as obese (body mass index 30). Conclusions: Although the AMPM accurately reported EIs in normal-weight subjects, research is warranted to enhance its accuracy in overweight and obese persons. Am J Clin Nutr2008;88: 324–32.

Diabetes mellitus and its sequelae are a major and growing public health problem. The prevalence of diabetes worldwide is 194 million persons, or 5.1% of the population, and is projected to increase to 333 million, or 6.3% of the population, by 2025. Type 2 diabetes accounts for approximately 90-95% of those with diabetes in the United States and other developed countries. Tea is the most widely consumed beverage in the world, second only to water. Tea contains polyphenols and other components that may reduce the risk of developing chronic diseases such as cardiovascular disease and cancer. Some evidence also shows that tea may affect glucose metabolism and insulin signaling, which, as a result, has spurred interest in the health effects of tea consumption on diabetes. Epidemiologic studies suggest some relation between tea consumption and a reduced risk of type 2 diabetes, although the mechanisms for these observations are uncertain. Findings from in vitro and animal models suggest that tea and its components may influence glucose metabolism and diabetes through several mechanisms, such as enhancing insulin sensitivity. Some human clinical studies evaluating tea and its components show improvement in glucoregulatory control and endothelial function. However, further controlled clinical trials are required to gain a better understanding of the long-term effects of tea consumption in persons with diabetes.

Background Activity monitors (AM) are small, electronic devices used to quantify the amount and intensity of physical activity (PA). Unfortunately, it has been demonstrated that data loss that occurs when AMs are not worn by subjects (removals during sleeping and waking hours) tend to result in biased estimates of PA and total energy expenditure (TEE). No study has reported the degree of data loss in a large study of adults, and/or the degree to which the estimates of PA and TEE are affected. Also, no study in adults has proposed a methodology to minimize the effects of AM removals. Methods Adherence estimates were generated from a pool of 524 women and men that wore AMs for 13 – 15 consecutive days. To simulate the effect of data loss due to AM removal, a reference dataset was first compiled from a subset consisting of 35 highly adherent subjects (24 HR; minimum of 20 hrs/day for seven consecutive days). AM removals were then simulated during sleep and between one and ten waking hours using this 24 HR dataset. Differences in the mean values for PA and TEE between the 24 HR reference dataset and the different simulations were compared using paired t-tests and/or coefficients of variation. Results The estimated average adherence of the pool of 524 subjects was 15.8 ± 3.4 hrs/day for approximately 11.7 ± 2.0 days. Simulated data loss due to AM removals during sleeping hours in the 24 HR database (n = 35), resulted in biased estimates of PA (p < 0.05), but not TEE. Losing as little as one hour of data from the 24 HR dataset during waking hours results in significant biases (p < 0.0001) and variability (coefficients of variation between 7 and 21%) in the estimates of PA. Inserting a constant value for sleep and imputing estimates for missing data during waking hours significantly improved the estimates of PA. Conclusion Although estimated adherence was good, measurements of PA can be improved by relatively simple imputation of missing AM data.

Background Understanding the relationships between physical activity (PA) and disease has become a major area of research interest. Activity monitors, devices that quantify free-living PA for prolonged periods of time (days or weeks), are increasingly being used to estimate PA. A range of different activity monitors brands are available for investigators to use, but little is known about how they respond to different levels of PA in the field, nor if data conversion between brands is possible. Methods 56 women and men were fitted with two different activity monitors, the Actigraph™ (Actigraph LLC; AGR) and the Actical™ (Mini-Mitter Co.; MM) for 15 days. Both activity monitors were fixed to an elasticized belt worn over the hip, with the anterior and posterior position of the activity monitors randomized. Differences between activity monitors and the validity of brand inter-conversion were measured by t-tests, Pearson correlations, Bland-Altman plots, and coefficients of variation (CV). Results The AGR detected a significantly greater amount of daily PA (216.2 ± 106.2 vs. 188.0 ± 101.1 counts/min, P < 0.0001). The average difference between activity monitors expressed as a CV were 3.1 and 15.5% for log-transformed and raw data, respectively. When a conversion equation was applied to convert datasets from one brand to another, the differences were no longer significant, with CV's of 2.2 and 11.7%, log-transformed and raw data, respectively. Conclusion Although activity monitors predict PA on the same scale (counts/min), the results between these two brands are not directly comparable. However, the data are comparable if a conversion equation is applied, with better results for log-transformed data.

An unresolved issue in the field of diet and health is if and how changes in meal frequency affect energy metabolism in humans. We therefore evaluated the influence of reduced meal frequency without a reduction in energy intake on glucose metabolism in normal-weight, healthy male and female subjects. The study was a randomized crossover design, with two 8-week treatment periods (with an intervening 11-week off-diet period) in which subjects consumed all of their calories for weight maintenance distributed in either 3 meals or 1 meal per day (consumed between 4:00 pm and 8:00 pm). Energy metabolism was evaluated at designated time points throughout the study by performing morning oral glucose tolerance tests and measuring levels of glucose, insulin, glucagon, leptin, ghrelin, adiponectin, resistin, and brain-derived neurotrophic factor (BDNF). Subjects consuming 1 meal per day exhibited higher morning fasting plasma glucose levels, greater and more sustained elevations of plasma glucose concentrations, and a delayed insulin response in the oral glucose tolerance test compared with subjects consuming 3 meals per day. Levels of ghrelin were elevated in response to the 1-meal-per-day regimen. Fasting levels of insulin, leptin, ghrelin, adiponectin, resistin, and BDNF were not significantly affected by meal frequency. Subjects consuming a single large daily meal exhibit elevated fasting glucose levels and impaired morning glucose tolerance associated with a delayed insulin response during a 2-month diet period compared with those consuming 3 meals per day. The impaired glucose tolerance was reversible and was not associated with alterations in the levels of adipokines or BDNF.

Dual-absorbance x-ray absorptiometry (DEXA) is a rapid method for body fat estimation that correlates well with more time-consuming, technically challenging “gold standard” methods, and is relative...

Background The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat, central and peripheral fat, and lean mass) in postmenopausal women. Methods This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis. Results and discussion In multivariate analysis, women who were overweight (BMI > 25 to ≤ 30 kg/m2) had a 2-fold increase, and obese women (BMI > 30 kg/m2) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI ≤25 kg/m2) women. When the models for the different measures of adiposity were assessed by multiple R2, models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance. Conclusion Under carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin.

Background: Both obesity and sex hormones are known risk factors for postmenopausal breast cancer. Although adiposity and sex hormones have been studied in the past, previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions. In this study, we investigated the usefulness of body mass index (BMI) as a sufficient adiposity measurement to assess associations with sex hormone levels. Methods: This study was conducted as a cross-sectional analysis within the control segment (0 g alcohol group) of a randomized, crossover design, in which 51 postmenopausal women consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks each as part of a controlled diet. Dual-energy X-ray absorptiometry scans were administered to the women during the control (0 g alcohol) segment, and a blood sample was drawn at the end of that diet period for hormone analysis. Results: In multivariate analysis (adjusted for age, race, family history of breast cancer, parity, and menarche 0.10) for these five analytes beyond that of BMI alone. Conclusions: In this population of postmenopausal women, under carefully controlled dietary conditions, we confirmed previous findings that higher levels of adiposity were associated with higher concentrations of estrogens and lower sex hormone-binding globulin, and we found that the use of the epidemiology-friendly BMI seems sufficient to assess associations with these hormone levels. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2502–7)

The imperative to address the national obesity epidemic has stimulated efforts to develop accurate dietary assessment methods suitable for large-scale applications. This study evaluated the performance of the USDA Automated Multiple-Pass Method (AMPM), the computerized dietary recall designed for the National Health and Nutrition Examination Survey dietary survey, and 2 epidemiological methods [the Block food-frequency questionnaire (Block) and National Cancer Institute's Diet History Questionnaire (DHQ)] using doubly labeled water (DLW) total energy expenditure (TEE) and 14-d estimated food record (FR) absolute nutrient intake as criterion measures. Twenty highly motivated, normal-weight-stable, premenopausal women participated in a free-living study that included 2 unannounced AMPM recalls and completion of the Block and DHQ. AMPM and FR total energy intake (TEI) did not differ significantly from DLW TEE [AMPM: 8982 +/- 2625 kJ; FR: 8416 +/- 2217; DLW: 8905 +/- 1881 (mean +/- SD)]. Conversely, the questionnaires underestimated TEI by approximately 28% (Block: 6365 +/- 2193; DHQ: 6215 +/- 1976; P < 0.0001 vs. DLW). Pearson correlation coefficients for DLW TEE with each dietary method TEI showed a stronger linear relation for AMPM (r = 0.53; P = 0.02) and FR (r = 0.41; P = 0.07) than for the Block (r = 0.25; P = 0.29) and DHQ (r = 0.15; P = 0.53). Most mean absolute FR nutrient intakes were closely approximated by the AMPM but were significantly underestimated by the questionnaires. In highly motivated premenopausal women, the AMPM provides valid measures of group total energy and nutrient intake whereas the Block and DHQ yield underestimations.

A double-blind, randomized clinical trial was conducted to determine the effects of supplemental whey protein, compared to soy protein and an isocaloric amount of carbohydrate, on body weight and c...

Alcohol consumption is linked to increased breast cancer risk. Since oestrogens increase breast cancer risk, possibly through oxidative damage, and we have shown that alcohol consumption increases serum oestrogens, we tested whether moderate alcohol supplementation increased oxidative DNA damage among healthy postmenopausal women not on hormone replacement therapy in a randomized controlled crossover study. We used serum 5-hydroxymethyl-2-deoxyuridine (5-HMdU) autoantibodies (aAbs) as a marker of oxidative DNA damage. The results showed no evidence for increased or decreased levels of oxidative DNA damage among women who consumed 15 g or 30 g alcohol per day for 8 weeks compared with women in the 0 g alcohol group. We conclude that among healthy women, it is possible that an 8-week trial of moderate alcohol supplementation might be too short to make enough 5-HMdU aAbs to compare differences by alcohol dose. In future studies, a panel of biomarkers for DNA damage should be used.

We explored whether serum leptin response to alcohol ingestion was related to common leptin receptor gene polymorphisms, K109R (Lys109Arg), Q223R (Gln223Arg), S343S [Ser(T)343Ser(C)], and K656N (Lys656Asn), of reported physiologic significance during a controlled intervention. Fifty-three participants rotated through three 8-week treatment periods and consumed 0, 15 (equivalent to one drink), or 30 g (equivalent to two drinks) of alcohol (95% ethanol in 12 ounces of orange juice) per day, in random order. During the controlled feeding periods, all food and beverages including alcoholic beverages were prepared and supplied by the staff of the Beltsville Human Nutrition Research Center's Human Study Facility (Beltsville, MD), and energy intake was adjusted to maintain a constant weight. Blood was collected after an overnight fast on 3 separate days during the last week of each controlled feeding period and pooled for hormone analysis. Circulating serum leptin concentration was measured in duplicate by RIA and genotype analysis was done on DNA extracted from WBC using real-time PCR analysis amplification (TaqMan). Linear mixed models with a single random intercept reflecting a participant effect were used to estimate changes in serum leptin levels at 15 and 30 g of alcohol per day relative to 0 g of alcohol per day. No significant effects were found between common leptin receptor polymorphisms and serum leptin levels (P ≥ 0.26).

Background: Increased circulating insulin-like growth factor I (IGF-I) concentrations, frequently adjusted for IGF binding protein 3 (IGFBP-3), have been associated with increased risk of several types of cancer, including colon, prostate, and breast. Studies have suggested that alcohol may affect IGF-I or IGFBP-3; however, controlled feeding studies to assess alcohol’s effects on IGF-I or IGFBP-3 have not been conducted. Objective: To determine whether chronic, moderate alcohol intake affects serum IGF-I or IGFBP-3 concentrations, we performed a controlled, crossover feeding study. Design: Fifty-three postmenopausal women were randomly assigned to consume 0 g (control), 15 g (one drink), or 30 g (2 drinks) alcohol daily for 8 wk and were rotated through the other 2 intake levels in random order. All foods and beverages were provided during the intervention. Individuals were monitored and calories adjustedtomaintainconstantweight,andserumwascollectedatthe end of each diet period. Results: Compared with the effects of 0 g alcohol/d, IGF-I concentrations were nearly unchanged by 15 g alcohol/d (0.8%; 95% CI: 3.2%, 3.5%) but decreased significantly by 4.9% (95% CI: 8.0%, 1.6%) with 30 g alcohol/d. IGFBP-3 concentrations significantly increased by 3.0% (95% CI: 0.4%, 5.6%) with 15 g alcohol/d but did not increase significantly with 30 g/d (1.8%; 95% CI: 0.9%, 4.5%). Conclusions: To our knowledge, this is the first published controlled diet study to find that in postmenopausal women, when weight is kept constant, alcohol consumption reduces the amount of serum IGF-I potentially available for receptor binding. These findingssuggestthattheeffectofalcoholintakeshouldbeconsideredin studies of IGF-I, IGFBP-3, and cancer in postmenopausal women. Am J Clin Nutr 2005;81:503–7.

Background We have demonstrated that moderate alcohol consumption (15 g/d, 30 g/d) for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. We now report on the relationships between serum estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) levels after 4 weeks of moderate alcohol supplementation, and compare the results to the 8 weeks data to elucidate time-to-effect differences. Methods Postmenopausal women (n = 51) consumed 0 (placebo), 15 (1 drink), and 30 (2 drinks) g alcohol (ethanol)/ day for 8 weeks as part of a controlled diet in a randomized crossover design. Blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Changes in estrone sulfate and DHEAS levels from placebo to 15 g and 30 g alcohol per day were estimated using linear mixed models. Results and Discussion At week 4, compared to the placebo, estrone sulfate increased an average 6.9% (P = 0.24) when the women consumed 15 g of alcohol per day, and 22.2% (P = 0.0006) when they consumed 30 g alcohol per day. DHEAS concentrations also increased significantly by an average of 8.0% (P < 0.0001) on 15 g of alcohol per day and 9.2% (P < 0.0001) when 30 g alcohol was consumed per day. Trend tests across doses for both estrone sulfate (P = 0.0006) and DHEAS (P < 0.0001) were significant. We found no significant differences between the absolute levels of serum estrone sulfate at week 4 versus week 8 (P = 0.32) across all doses. However, absolute DHEAS levels increased from week 4 to week 8 (P < 0.0001) at all three dose levels. Conclusions These data indicate that the hormonal effects due to moderate alcohol consumption are seen early, within 4 weeks of initiation of ingestion.

Background: The effect of individual dietary fatty acids on emerging risk factors for cardiovascular disease that are associated with subclinical inflammation is unknown. Objective: The goal was to evaluate the role of dietary fat and specific fatty acids, especially trans fatty acids, in altering concentrations of markers of inflammation in humans fed controlled diets. Design: In a randomized crossover design, 50 men consumed controlled diets for 5 wk that provided 15% of energy from protein, 39% of energy from fat, and 46% of energy from carbohydrate. Eight percent of fat or fatty acids was replaced across diets with the following: cholesterol, oleic acid, trans fatty acids (TFAs), stearic acid (STE), TFASTE (4% of energy each), and 12:0 –16:0 saturated fatty acids (LMP). Results: Fibrinogen concentrations were higher after consumption of the diet enriched in stearic acid than after consumption of the carbohydrate diet. C-reactive protein concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet, but were not significantly different after consumption of the TFA and TFASTE diets than after consumption of the LMP diet. Interleukin 6 concentrations were lower after consumption of the oleic acid diet than after consumption of the LMP, TFA, and STE diets. E-selectin concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet. Consumption of the TFA but not the TFASTE diet resulted in higher E-selectin concentrations than did the LMP diet. Conclusions: These data provide evidence that dietary fatty acids can modulate markers of inflammation. Although stearic acid minimally affects LDL cholesterol, it does appear to increase fibrinogen concentrations. Am J Clin Nutr 2004;79:969 –73.

We examined serum leptin levels in a controlled feeding and alcohol ingestion study to elucidate potential mechanisms by which alcohol may affect cancer and immunologically related health risks. A total of 53 healthy, nonsmoking postmenopausal women completed a random-order, three-period crossover design study in which each woman received zero (0 g of alcohol), one (15 g of alcohol), or two (30 g alcohol) drinks per day. After accounting for differences in body mass index, women who consumed 15 or 30 g of alcohol per day had 7.3% (95% confidence interval [CI] = 3.0% to 15.1%) and 8.9% (95% CI = 1.6% to 16.7%) higher serum leptin levels, respectively (P(trend) =.018), than women who consumed 0 g of alcohol per day. Younger women (i.e., 49-54 years) demonstrated a statistically significantly larger association of alcohol consumption level with the increase in serum leptin levels than older women (i.e., 55-79 years) (24.4%, 95% CI = 9.3% to 42.0% versus 3.7%, 95% CI = -4.1% to 12.1% increase in serum leptin levels for 30 g of alcohol per day relative to 0 g of alcohol per day for the lowest age quartile compared with the three highest age quartiles combined; P =.022). These results indicate that moderate alcohol consumption (15-30 g of alcohol per day) increases serum leptin levels in postmenopausal women and may predispose moderate drinkers to the morbidities associated with chronic elevations of this hormone including cancer.

This study was designed to test whether daily alcohol intake can influence parameters related to rate of alcohol clearance and systemic alcohol exposure.Postmenopausal women (N = 14) completed a study in which they consumed an alcohol treatment daily for 8 weeks. In a three-period crossover design, women consumed 0, 15 or 30 g/day ethanol, with each subject completing each treatment level. Following the 8-week adaptation period, the subjects consumed a single dose of 15 g ethanol, and breath samples collected to assess breath alcohol concentration (BrAC) every 5 minutes until the BrAC declined to zero.Adaptation to daily alcohol intake of 30 g/day resulted in reduced breath alcohol response compared to adaptation to 0 g/day. Specifically, area under the BrAC time curve was lower after women had consumed 30 g ethanol per day compared to that after daily consumption of 0 grams per day. Also, the time required for BrAC to decline to 0.01% after the bolus dose was reduced when subjects were adapted to 30g/day compared to 0 g/day.Daily intake of alcohol at a level of 30 g/day appears to be sufficient to alter the parameters related to systemic alcohol exposure.

Background: Reduced bone mass is common in both children and adults with cystic fibrosis (CF) and may be a consequence of inadequate calcium absorption. The effect of CF on intestinal calcium absorption and retention has not been described in children. Objective: Calcium absorption and urinary losses were characterized in clinically stable girls with CF consuming self-selected diets and following usual pancreatic enzyme regimens. Design: The percentage of calcium absorption was assessed in 23 girls (aged 7‐18 y) with CF by using oral ( 44 Ca) and intravenous ( 42 Ca) stable isotopes. Girls were grouped according to Tanner stage of breast development. True calcium absorption (Va) was determined as the product of percentage calcium absorption and average 4-d daily calcium intake. Calcium balance was estimated by subtracting urinary calcium and estimated endogenous fecal losses from the measure of Va. Analysis of variance was used to compare outcomes among pubertal groups, and regression analysis was used to describe the relations of percentage and total calcium absorption to calcium intake and of urinary calcium to sodium excretion. Results: Percentage calcium absorption was inversely related to calcium intake. Percentage absorption and Va were similar to values observed in healthy girls in other studies. Total calcium absorption and estimated calcium balance were significantly greater among girls in early puberty (Tanner stages 2‐3) than in prepubertal or late-pubertal girls (P < 0.05). Urinary calcium was positively related to urinary sodium excretion (P = 0.02). Conclusion: The efficiency of calcium absorption was not compromised in clinically stable girls with CF. Am J Clin Nutr 2003;78:110‐6.

ContextEpidemiologic data demonstrate that moderate alcohol intake is associated with improved insulin sensitivity in nondiabetic individuals. No controlled-diet studies have addressed the effects of daily moderate alcohol consumption on fasting insulin and glucose concentrations and insulin sensitivity.ObjectiveTo determine whether daily consumption of low to moderate amounts of alcohol influences fasting insulin and glucose concentrations and insulin sensitivity in nondiabetic postmenopausal women.Design, Setting, and ParticipantsRandomized controlled crossover trial of 63 healthy postmenopausal women, conducted at a clinical research center in Maryland between 1998 and 1999.InterventionsParticipants were randomly assigned to consume 0, 15, or 30 g/d of alcohol for 8 weeks each as part of a controlled diet. All foods and beverages were provided during the intervention. An isocaloric beverage was provided in the 0-g/d arm. Energy intake was adjusted to maintain constant body weight.Main Outcome MeasuresFasting insulin, triglyceride, and glucose concentrations, measured at the end of each dietary period; insulin sensitivity, estimated with a published index of glucose disposal rate corrected for fat-free mass based on fasting insulin and fasting triglyceride concentrations, compared among treatments with a mixed-model analysis of variance.ResultsA complete set of plasma samples was collected and analyzed for 51 women who completed all diet treatments. Consumption of 30 g/d of alcohol compared with 0 g/d reduced fasting insulin concentration by 19.2% (P = .004) and triglyceride concentration by 10.3% (P = .001), and increased insulin sensitivity by 7.2% (P = .002). Normal-weight, overweight, and obese individuals responded similarly. Only fasting triglyceride concentration was significantly reduced when comparing 0 and 15 g/d of alcohol (7.8%; P = .03), and no difference was found between consumption of 15 and 30 g/d of alcohol; however, there was a significant linear trend (P = .001). Fasting glucose concentrations were not different across treatments.ConclusionsConsumption of 30 g/d of alcohol (2 drinks per day) has beneficial effects on insulin and triglyceride concentrations and insulin sensitivity in nondiabetic postmenopausal women.