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    About

American Journal of Clinical Nutrition

Oxford University Press

1954-

ISSN: 0002-9165 (1938-3207)
Nutrition & Dietetics - Nutrition and Dietetics - Medicine (miscellaneous)

Recent articles

1 show abstract
0002-9165 * 1938-3207 * 29607803

ABSTRACT
BackgroundA higher protein intake is suggested to preserve muscle mass during aging and may therefore reduce the risk of sarcopenia.ObjectivesWe explored whether the amount and type (animal or vegetable) of protein intake were associated with 5-y change in mid-thigh muscle cross-sectional area (CSA) in older adults (n = 1561).MethodsProtein intake was assessed at year 2 by a Block food-frequency questionnaire in participants (aged 70–79 y) of the Health, Aging, and Body Composition (Health ABC) Study, a prospective cohort study. At year 1 and year 6 mid-thigh muscle CSA in square centimeters was measured by computed tomography. Multiple linear regression analysis was used to examine the association between energy-adjusted protein residuals in grams per day (total, animal, and vegetable protein) and muscle CSA at year 6, adjusted for muscle CSA at year 1 and potential confounders including prevalent health conditions, physical activity, and 5-y change in fat mass.ResultsMean (95% CI) protein intake was 0.90 (0.88, 0.92) g · kg–1 · d–1 and mean (95% CI) 5-y change in muscle CSA was −9.8 (−10.6, −8.9) cm2. No association was observed between energy-adjusted total (β = −0.00; 95% CI: −0.06, 0.06 cm2; P = 0.982), animal (β = −0.00; 95% CI: −0.06, 0.05 cm2; P = 0.923), or plant (β = +0.07; 95% CI: −0.06, 0.21 cm2; P = 0.276) protein intake and muscle CSA at year 6, adjusted for baseline mid-thigh muscle CSA and potential confounders.ConclusionsThis study suggests that a higher total, animal, or vegetable protein intake is not associated with 5-y change in mid-thigh muscle CSA in older adults. This conclusion contradicts some, but not all, previous research. This trial was registered at www.trialregister.nl as NTR6930.
2 show abstract
0002-9165 * 1938-3207 * 29607804

Article URL: https://academic.oup.com/ajcn/article/109/3/684/5372514?rss=1
Citation: Vol 109 No. 3 (2019) pp 684 684
Publication Date: Fri, 08 Mar 2019 00:00:00 GMT
Journal: American Journal of Clinical Nutrition
3 show abstract
0002-9165 * 1938-3207 * 29607805

ABSTRACT
BackgroundSarcopenia and low skeletal muscle radiodensity (SMD) have been associated with adverse outcomes in patients with colorectal cancer (CRC); however, factors contributing to these 2 muscle abnormalities are unclear.ObjectivesThe aim of this study was to investigate the association of medical and demographic characteristics with muscle abnormalities among patients with nonmetastatic CRC.MethodsPatients with stage I–III invasive CRC (2006–11) who had diagnostic computed tomography (CT) available from Kaiser Permanente Northern California electronic medical records were included. CT-assessed sarcopenia and low SMD were defined according to optimal stratification. Logistic regressions including age, stage, site, total adipose tissue (TAT), race/ethnicity, neutrophil-lymphocyte ratio, smoking history, alcohol use, and Charlson Comorbidity Score were performed to identify characteristics associated with muscle abnormalities.ResultsThe study included 3262 patients (49.9% females) with a mean ± SD age of 62.6 ± 11.4 y. Sarcopenia and low SMD were highly prevalent (42.4% and 29.6%, respectively). Age and sex interactions were noted for muscle mass, but not SMD. Age was associated with higher odds of muscle abnormalities in a dose-response manner. Compared with those aged ≤50 y, patients aged 70–80 y had considerably higher odds (OR: 6.19; 95% CI: 4.72, 8.11) of sarcopenia, and low SMD (OR: 17.81; 95% CI: 11.73, 27.03). High TAT was related to a higher odds of low SMD (OR: 9.62; 95% CI: 7.37, 12.56), but lower odds of sarcopenia (OR: 0.59; 95% CI: 0.48, 0.71). Compared with Caucasians, African Americans had lower odds of sarcopenia and low SMD. Patients with a higher neutrophil-lymphocyte ratio had higher odds of having both muscle abnormalities. Patients who were smokers or had any comorbidity had higher odds of low SMD, but not sarcopenia.ConclusionsMuscle abnormalities were common in patients with nonmetastatic CRC, with great variability in muscle mass and SMD across age, TAT, and race/ethnicity. Factors associated with muscle abnormalities may be used to facilitate risk stratification and the guidance of targeted strategies to counteract these abnormalities.
4 show abstract
0002-9165 * 1938-3207 * 29607806

ABSTRACT
BackgroundThe risk of neural tube defects (NTDs) is influenced by nutritional factors and genetic determinants of one-carbon metabolism. A key pathway of this metabolism is the vitamin B-12– and folate-dependent remethylation of homocysteine, which depends on methionine synthase (MS, encoded by MTR), methionine synthase reductase, and methylenetetrahydrofolate reductase. Methionine, the product of this pathway, is the direct precursor of S-adenosylmethionine (SAM), the universal methyl donor needed for epigenetic mechanisms.ObjectivesThis study aimed to evaluate whether the availability of vitamin B-12 and folate and the expression or activity of the target enzymes of the remethylation pathway are involved in NTD risk.MethodsWe studied folate and vitamin B-12 concentrations and activity, expression, and gene variants of the 3 enzymes in liver from 14 NTD and 16 non-NTD fetuses. We replicated the main findings in cord blood from pregnancies of 41 NTD fetuses compared with 21 fetuses with polymalformations (metabolic and genetic findings) and 375 control pregnancies (genetic findings).ResultsThe tissue concentration of vitamin B-12 (P = 0.003), but not folate, and the activity (P = 0.001), transcriptional level (P = 0.016), and protein expression (P = 0.003) of MS were decreased and the truncated inactive isoforms of MS were increased in NTD livers. SAM was significantly correlated with MS activity and vitamin B-12. A gene variant in exon 1 of GIF (Gastric Intrinsic Factor gene) was associated with a dramatic decrease of liver vitamin B-12 in 2 cases. We confirmed the decreased vitamin B-12 in cord blood from NTD pregnancies. A gene variant of GIF exon 3 was associated with NTD risk.ConclusionsThe decreased vitamin B-12 in liver and cord blood and decreased expression and activity of MS in liver point out the impaired remethylation pathway as hallmarks associated with NTD risk. We suggest evaluating vitamin B-12 in the nutritional recommendations for prevention of NTD risk beside folate fortification or supplementation.
5 show abstract
0002-9165 * 1938-3207 * 29607807

ABSTRACT
BackgroundCoffee is one of the most widely consumed stimulants worldwide and is generally considered to be safe or even beneficial for health. However, increased risk of myocardial infarction and hypertension has been suggested for individuals who carry a functional variant at cytochrome P450 1A2 (CYP1A2), which makes them less effective at metabolizing caffeine.ObjectivesThe aim of this study was to examine if the CYP1A2 genotype or a genetic score for caffeine metabolism (caffeine-GS) modifies the association between habitual coffee consumption and the risk of cardiovascular disease (CVD).MethodsGenetic data and information on habitual coffee intake and relevant covariates were available for 347,077 individuals in the UK Biobank, including 8368 incident CVD cases. We used logistic regression to test for the association between coffee intake and CVD risk, and whether the association varies with CYP1A2 genotype or caffeine-GS.ResultsThe association between habitual coffee intake and CVD risk was nonlinear, and, compared with participants drinking 1–2 cups/day, the risk of CVD was elevated for nondrinkers, drinkers of decaffeinated coffee, and those who reported drinking >6 cups/day (increase in odds by 11%, 7%, and 22%, respectively, P-curvature = 0.013). CYP1A2 genotype and caffeine-GS were not associated with CVD (P ≥ 0.22 for all comparisons). There was no evidence for an interaction between the CYP1A2 genotype or caffeine-GS and coffee intake with respect to risk of CVD (P ≥ 0.53).ConclusionsHeavy coffee consumption was associated with a modest increase in CVD risk, but this association was unaffected by genetic variants influencing caffeine metabolism.
6 show abstract
0002-9165 * 1938-3207 * 29607808

ABSTRACTThe use of neuroimaging tools, especially functional magnetic resonance imaging, in nutritional research has increased substantially over the past 2 decades. Neuroimaging is a research tool with great potential impact on the field of nutrition, but to achieve that potential, appropriate use of techniques and interpretation of neuroimaging results is necessary. In this article, we present guidelines for good methodological practice in functional magnetic resonance imaging studies and flag specific limitations in the hope of helping researchers to make the most of neuroimaging tools and avoid potential pitfalls. We highlight specific considerations for food-related studies, such as how to adjust statistically for common confounders, like, for example, hunger state, menstrual phase, and BMI, as well as how to optimally match different types of food stimuli. Finally, we summarize current research needs and future directions, such as the use of prospective designs and more realistic paradigms for studying eating behavior.
7 show abstract
0002-9165 * 1938-3207 * 29607809

ABSTRACT
BackgroundCoffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood.ObjectivesThe aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases.MethodsWe investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone–binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses’ Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors.ResultsCompared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (−8.7%), IGFBP-3 (−2.2%), estrone (−6.4%), total estradiol (−5.7%), free estradiol (−8.1%), leptin (−6.4%), CRP (−16.6%), IL-6 (−8.1%), and sTNFR-2 (−5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee.ConclusionOur data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.
8 show abstract
0002-9165 * 1938-3207 * 29607810

ABSTRACT
BackgroundSoy-based dietary supplements have been promoted as natural alternatives to menopausal hormone therapy, but their potential effect on breast cancer development is controversial.ObjectivesWe examined the relation between the consumption of soy supplements and the risk of breast cancer, overall and by tumor hormone receptor status, among women aged >50 y.MethodsIn total, 76,442 women from the Etude Epidemiologique aupres de Femmes de la Mutuelle Generale de l’Education Nationale (E3N) cohort, born between 1925 and 1950, were followed from 2000 to 2011 (11.2 y on average, starting at a mean age of 59.5 y; 3608 incident breast cancers), with soy supplement use assessed every 2–3 y. HRs of breast cancer were estimated with the use of multivariable Cox models.ResultsCompared with never using soy supplements, the HRs associated with current use of soy supplements were 0.92 (95% CI: 0.76, 1.11) for all, 0.78 (95% CI: 0.60, 0.99) for estrogen receptor (ER)–positive, and 2.01 (95% CI: 1.41, 2.86) for ER-negative breast cancers. There was no association between past use of soy supplements and breast cancer. HRs for current use were 1.36 (95% CI: 0.95, 1.93) and 0.82 (95% CI: 0.65, 1.02) among women with and without a family history of breast cancer, respectively (P-interaction = 0.03) and 1.06 (95% CI: 0.87, 1.30) ≥5 y after menopause compared with 0.50 (95% CI: 0.31, 0.81) in premenopause or ≤5 y postmenopause (P-interaction = 0.04).ConclusionsIn this cohort of women aged >50 y, we report opposing associations of soy supplements with ER-positive and ER-negative breast cancer risk. Our results also caution against the use of these supplements in women with a family history of breast cancer. Whether the risk profile of soy supplements could be more favorable among premenopausal or recently postmenopausal women deserves further investigation.
9 show abstract
0002-9165 * 1938-3207 * 29607811

ABSTRACT
BackgroundDietary choline is a precursor of trimethylamine N-oxide (TMAO), a metabolite that has been associated with an increased risk of cardiovascular disease. The mechanism underlying this association is unknown, but may include TMAO effects on blood pressure (BP).ObjectivesThis study assessed the association of choline intake with hypertension and BP in US adults through the use of NHANES 2007–2010 data.MethodsThis cross-sectional study was conducted in nonpregnant individuals aged ≥20 y. Choline intake was assessed with the use of two 24-h recalls. Outcomes were BP and hypertension status, which was assessed through the use of questionnaires and BP measurements. Modifying factors (e.g., sex, race/ethnicity) and dietary compared with supplemental sources of choline intake were also investigated.ResultsThe associations of total (dietary + supplementaldietary + supplemental) and dietary choline intake with the prevalence odds of hypertension differed by sex (n = 9227; P-interaction = 0.04 and 0.03, respectively). In women, both total and dietary choline intake tended to be inversely associated with hypertension (n = 4748; prevalence OR per 100 mg of choline intake: 0.89; 95% CI: 0.77, 1.02; P < 0.10 for both total and dietary choline). No association was observed in men (n = 4479; P = 0.54 and 0.49 for total choline and dietary choline, respectively). Use of choline supplements was inversely associated with hypertension in both sexes (user compared with nonuser; OR: 0.68; 95% CI: 0.49, 0.92; P = 0.01). There was little to no association of total, dietary, or supplemental choline intake with systolic or diastolic BP (n = 6,554; the mean ± SEM change in BP associated with a 100-mg difference in total choline was −0.26 ± 0.22 mm Hg for systolic BP and −0.29 ± 0.19 mm Hg for diastolic BP).ConclusionsCross-sectional NHANES data do not support the hypothesis of a positive association between choline intake and BP.
10 show abstract
0002-9165 * 1938-3207 * 29607812
Coffee is a major source of caffeine, one of the most widely consumed stimulants in the world. Coffee also contains many other substances, such as polyphenols, diterpenoids, and trace minerals, that have been linked to various health conditions. The consumption of either caffeinated or decaffeinated coffee has been associated with increases and decreases in the risk of a number of chronic diseases. In the present issue of the Journal, Hang et al. (1) used several biomarkers to explore potential mechanisms underlying the putative protective effects of coffee in 2 large, well-characterized cohorts: the Nurses’ Health Study and the Health Professionals Follow-Up Study. They found that coffee consumption was associated with favorable profiles of several biomarkers in key metabolic and inflammatory pathways, including some that are specifically linked to cardiovascular disease. Many of the associations observed were similar for caffeinated and decaffeinated coffee, suggesting that the effects are not due to caffeine. Moreover, it appears that anti-inflammatory pathways might be driving many of the health-related effects of coffee. What remains unknown, however, is what components of coffee confer such benefits. One approach that can be used to home in on the relevant bioactive(s) is to include genetic variants affecting the metabolism or response to those bioactives, as proposed over a decade ago (2). Indeed, another study in this issue of the Journal did just that. Using prospective data from the UK Biobank, Zhou and Hypponen (3) evaluated the association between habitual coffee consumption and cardiovascular disease risk, and incorporated genetic markers of caffeine metabolism to determine the contribution of caffeine to this association. The authors identified a U-shaped association between coffee intake and cardiovascular disease that was not modified by the genetic markers tested. These findings contrast those of Cornelis et al. (4), who first reported that variation in cytochrome P450 family 1 subfamily A member 2 (CYP1A2), which affects the rate of caffeine metabolism and modifies the association between coffee consumption and the risk of myocardial infarction. Those earlier findings have since been extended to hypertension (5), impaired fasting glucose (6), and blood pressure (7), where in all cases coffee or caffeine was associated with adverse outcomes only in individuals with the CYP1A2 genotype associated with slow metabolism of caffeine. As such, the lack of a modifying effect of genetic differences in caffeine metabolism observed by Zhou and Hypponen seems unexpected (3). A recent study that used the same UK Biobank population found that coffee is inversely associated with overall mortality regardless of genetic differences affecting caffeine metabolism, although the association was only marginally significant for cardiovascular mortality (8). The disparate findings between the 2 studies (3, 8), despite using data from the same UK Biobank cohort and incorporating similar genetic risk scores based on the same genome-wide association study (9), is puzzling. Importantly, both studies have significant limitations that preclude a definitive conclusion about the role of genetics in modifying the association between coffee and health. For instance, Loftfield et al. (8) included decaffeinated coffee in the analyses, thus attenuating any effects of genetic differences in caffeine metabolism on the outcomes measured. Although both studies examined the role of CYP1A2, they also used genetic risk scores that have yet to be shown to predict differences in the rate of caffeine metabolism (3, 8). They also did not consider all sources of caffeine, which results in misclassification of the exposure of interest. Zhou and Hypponen (3) state that their prospective analysis minimizes the possibility of reverse causation. However, such a design reflects long-term intake, and coffee has distinct acute effects on cardiovascular phenotypes, such as blood pressure, that may affect its contribution to cardiovascular outcomes (10). Acute effects are better captured by case-control (4), or intervention (7), study designs. The previous study, showing that CYP1A2 modifies the association between coffee and myocardial infarction, found the effect was greatest in younger cases (4), suggesting an important modifying effect of age and that a lack of effect in an older cohort could be due to a healthy survivor effect. The authors found that a gene-coffee-age interaction did not reach the threshold for significance (P ≥ 0.11, data not shown), but a stratified analysis by median age should have been shown considering previous findings (4). As such, the modifying effects of CYP1A2 cannot be ruled out. Future studies that aim to focus on caffeine by incorporating the CYP1A2 genotype into the study design, as Zhou and Hypponen have done, must also include all sources of this bioactive. Otherwise, any estimate of the modifying effect of genetics will be affected by the imprecise estimate of exposure to caffeine. Studies that seek to better understand the role of other bioactives in coffee would be greatly strengthened by incorporating genetic variants that affect their metabolism or are potential targets of their action (2).
11 show abstract
0002-9165 * 1938-3207 * 29607813

ABSTRACT
BackgroundWhich blood-based indicator best reflects the iron status in pregnant women is unclear. Better assessments of iron status in today's multiethnic populations are needed to optimize treatment and clinical recommendations.ObjectivesWe aimed to determine the prevalence of anemia (hemoglobin <11.0 g/dL in first and <10.5 g/dL in second trimester) and iron deficiency (ID) by the iron indicators serum ferritin <15 µg/L, serum soluble transferrin receptor (sTfR) >4.4 mg/L, and calculated total body iron <0 mg/kg, and their associations with ethnicity.MethodsThis was a population-based cross-sectional study from primary antenatal care of 792 healthy women in early pregnancy in Oslo, Norway. We categorized the women into 6 ethnic groups: Western European, South Asian, Middle Eastern, Sub-Saharan African, East Asian, and Eastern European.ResultsAnemia was found in 5.9% of women (Western Europeans: 1.8%; non-Western: 0–14%, P < 0.05). ID from ferritin was found in 33% (Western Europeans: 15%; non-Western: 27–55%, P < 0.05). ID from sTfR was found in 6.5% (Western Europeans: 0.3%; non-Western: 0–20%, P < 0.01). Calculated total body iron indicated ID in 11% (Western Europeans: 0.6%, non-Western: 7.0–28%, P < 0.01). The prevalence of ID was significantly higher by all measures in South Asian, Sub-Saharan African, and Middle Eastern than in Western European women, and the ethnic differences persisted after adjusting for confounders. South Asians, Sub-Saharan Africans, and Middle Easterners had lower iron concentrations by all measures for all hemoglobin intervals. Anemia related to ID varied from 35% (sTfR) to 46% (total body iron) and 72% (ferritin) depending on the iron indicator used.ConclusionsWomen at the highest risk of ID and anemia were of South Asian, Middle Eastern, and Sub-Saharan African origin. The prevalence of ID differed considerably depending on the iron indicator used.
12 show abstract
0002-9165 * 1938-3207 * 29607814

ABSTRACT
BackgroundGrowing Up Milk (GUM) was developed to assist young children in meeting their nutritional requirements during the second year of life. However, there is limited evidence that GUM improves nutritional status and growth in young children.ObjectivesTo evaluate the effect of consuming Growing Up Milk “Lite” (GUMLi) (reduced protein with synbiotics and micronutrients added) compared with standard cow milk as part of a whole diet for 1 y on body composition at 2 y of age.MethodsGUMLi Trial was a multicenter, double-blind, randomized placebo-controlled trial conducted in Auckland and Brisbane. Healthy 1-y-olds were recruited and randomly assigned to receive either GUMLi or standard cow milk for 12 mo as part of a whole diet. The primary outcome was percentage body fat at 2 y of age measured by bioelectrical impedance. All regression models adjusted for baseline outcome and study center.Results160 children (80 per arm) were randomly assigned, and 134 (67 per arm) were included in the modified intention-to-treat analyses. The mean percentage body fat at 12 mo was 23.3% (SD 7.9) in the GUMLi group and 25.7% (SD 7.2) in the cow milk group. After adjusting for baseline outcome and study location, the estimated mean difference in percentage body fat between the intervention and control at 12 mo was −2.19% (95% CI: −4.24, −0.15; P = 0.036). Per-protocol analysis showed a similar effect (mean difference: −2.09%; 95% CI: −4.16, −0.03; P = 0.047). Both fat mass and the fat mass index were significantly lower in the GUMLi group at 12 mo than in the cow milk group.ConclusionsAt 2 y of age, children who consumed a GUM with a lower protein content than cow milk over 12 mo had a lower percentage of body fat. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12614000918628.
13 show abstract
0002-9165 * 1938-3207 * 29607815

ABSTRACT
BackgroundEstablishing healthy dietary habits during adolescence and young adulthood is critical for long-term health.ObjectivesThis study assessed the prevalence of meeting US Dietary Guidelines and trajectories in dietary intake for 4 MyPlate food groups during the transition from adolescence to young adulthood.MethodsThree waves of surveys and food frequency questionnaires were collected as part of Project EAT (Eating and Activity in Teens and Young Adults), a 15-y longitudinal study. Adolescents (n = 1177, 57% female, mean ± SD age 15.0 ± 1.5 y) were recruited in 1998–1999 in Minneapolis-St Paul, Minnesota public schools and were resurveyed twice in young adulthood at mean ± SD ages 25.3 ± 1.5 and 31.1 ± 1.5 y. The prevalence of meeting guidelines for each MyPlate food group was calculated at each time point. Mean daily servings were compared over 5 y in young adulthood through the use of paired t tests. Adjusted least-squares means were calculated to compare dietary intake in young adulthood across quartiles of adolescent intake.ResultsAdolescents had the highest prevalence of meeting dietary guidelines for fruit (37% for females and 30% for males) and dairy (53% for females and 61% for males); young adults >30 y had the highest prevalence of meeting dietary guidelines for vegetables (19% for females and 8% for males) and whole grains (23% for females and 17% for males). From the mid-twenties to early thirties, vegetable intake increased, whereas dairy intake decreased. Dietary intake generally tracked over time with individuals in the lower quartiles of intake at adolescence generally continuing to have low intake in young adulthood.ConclusionsAlthough the prevalence of meeting dietary guidelines for whole grains and vegetables, and daily servings of vegetables increased with age, improving intake of whole fruit, whole grains, dairy, and vegetables remains key during the transition from adolescence to young adulthood.
14 show abstract
0002-9165 * 1938-3207 * 29607816

ABSTRACT
BackgroundInsulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D).ObjectivesThe aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D.MethodsWe used a case-cohort study nested within the Prevención con Dieta Mediterránea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography–tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR–related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models.ResultsWe identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline [0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73)] and during a 1-y period [0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62)]. The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous) at baseline were 2.00 (95% CI: 1.58, 2.55) and 2.24 (95% CI: 1.72, 2.90), respectively, after adjustment for T2D risk factors.ConclusionsThe multimetabolite model identified in our study notably improved the predictive ability for HOMA-IR beyond classical risk factors and significantly predicted the risk of T2D.
15 show abstract
0002-9165 * 1938-3207 * 29607817

ABSTRACT
BackgroundAccurate assessment of energy expenditure may support weight-management recommendations. Measuring energy expenditure for each postpartum woman is unfeasible; therefore, accurate predictive equations are needed.ObjectivesThis study compared measured with predicted resting energy expenditure (REE) and total energy expenditure (TEE) in postpartum women.MethodsThis was a longitudinal observational study. REE was measured at 3 mo postpartum (n = 52) and 9 mo postpartum (n = 49), whereas TEE was measured once at 9 mo postpartum (n = 43) by whole body calorimetry (WBC). Measured REE (REEWBC) was compared with 17 predictive equations; measured TEE plus breast milk energy output (ERWBC) was compared with the estimated energy requirements/Dietary Reference Intakes equation (EERDRI). Fat and fat-free mass were measured by dual-energy X-ray absorptiometry. Group-level agreement was assessed by the Pearson correlation, paired t test, and Bland-Altman (bias) analyses. Individual-level accuracy was assessed with the use of Bland-Altman limits of agreement, and by the percentage of women with predicted energy expenditure within 10% of measured values (“accuracy”).ResultsThe cohort was primarily Caucasian (90%). At a group level, the best equation predicting REEWBC was the DRI at 3 mo postpartum (–7 kcal, –0.1%; absolute and percentage bias, respectively), and the Harris-Benedict at 9 mo postpartum (–17 kcal, –0.5%). At an individual level, the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) height and weight equation was the most accurate at 3 mo postpartum (100% accuracy) and 9 mo postpartum (98% accuracy), with the smallest limits of agreement. Equations including body composition variables were not more accurate. Compared with ERWBC, EERDRI bias was –36 kcal, with inaccurate predictions in 33% of women.ConclusionsMany REE predictive equations were accurate for group assessment, with the FAO/WHO/UNU height and weight equation having the highest accuracy for individuals. EERDRI performed well at a group level, but inaccurately for 33% of women. A greater understanding of the physiology driving energy expenditure in the postpartum period is needed to better predict TEE and ultimately guide effective weight-management recommendations.
16 show abstract
0002-9165 * 1938-3207 * 29607818

ABSTRACT
BackgroundPatients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF.ObjectivesThe primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations.MethodsThis was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%).ResultsA total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin.ConclusionsVitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256.
17 show abstract
0002-9165 * 1938-3207 * 29607819

ABSTRACT
BackgroundLipid droplets in human milk have a mode diameter of ∼4 μm and are surrounded by a native phospholipid-rich membrane. Current infant milk formulas (IMFs) contain small lipid droplets (mode diameter ∼0.5 μm) primarily coated by proteins. A concept IMF was developed mimicking more closely the structure and composition of human milk lipid droplets.ObjectivesThis randomized, controlled, double-blind equivalence trial evaluates the safety and tolerance of a concept IMF with large, milk phospholipid–coated lipid droplets (mode diameter 3–5 μm) containing vegetable and dairy lipids in healthy, term infants.MethodsFully formula-fed infants were enrolled up to 35 d of age and randomly assigned to 1 of 2 formulas until 17 wk of age: 1) Control IMF with small lipid droplets containing vegetable oils (n = 108); or 2) Concept IMF with large, milk phospholipid–coated lipid droplets comprised of 48% dairy lipids (n = 115). A group of 88 breastfed infants served as reference. Primary outcome was daily weight gain during intervention. Additionally, number and type of adverse events, growth, and tolerance parameters were monitored.ResultsEquivalence of daily weight gain was demonstrated (Concept compared with Control IMF: −1.37 g/d; 90% CI: −2.71, −0.02; equivalence margin ± 3 g/d). No relevant group differences were observed in growth, tolerance and number, severity, or relatedness of adverse events. We did observe a higher prevalence of watery stools in the Concept than in the Control IMF group between 5 and 12 wk of age (P < 0.001), closer to the stool characteristics observed in the breastfed group.ConclusionsAn infant formula with large, milk phospholipid–coated lipid droplets containing dairy lipids is safe, well tolerated, and supports an adequate growth in healthy infants. This trial was registered in the Dutch Trial Register (www.trialregister.nl) as NTR3683.
18 show abstract
0002-9165 * 1938-3207 * 29607820

ABSTRACTMissing data ubiquitously occur in randomized controlled trials and may compromise the causal inference if inappropriately handled. Some problematic missing data methods such as complete case (CC) analysis and last-observation-carried-forward (LOCF) are unfortunately still common in nutrition trials. This situation is partially caused by investigator confusion on missing data assumptions for different methods. In this statistical guidance, we provide a brief introduction of missing data mechanisms and the unreasonable assumptions that underlie CC and LOCF and recommend 2 appropriate missing data methods: multiple imputation and full information maximum likelihood.
19 show abstract
0002-9165 * 1938-3207 * 29607821

ABSTRACT
BackgroundGlutamine is the primary fuel for the gastrointestinal epithelium and maintains the mucosal structure. Oncologists frequently encounter oral mucositis, which can cause unplanned breaks in radiotherapy (RT).ObjectivesThe aim of this study was to explore the association between oral glutamine and acute toxicities in patients with head and neck cancer undergoing RT.MethodsThis was a parallel, double-blind, randomized, placebo-controlled Phase III trial conducted in a university hospital. A central randomization center used computer-generated tables to allocate interventions to 71 patients with stages I–IV head and neck cancers. The patients, care providers, and investigators were blinded to the group assignment. Eligible patients received either oral glutamine (5 g glutamine and 10 g maltodextrin) or placebo (15 g maltodextrin) 3 times daily from 7 d before RT to 14 d after RT. The primary and secondary endpoints were radiation-induced oral mucositis and neck dermatitis, respectively. These were documented in agreement with the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.ResultsThe study included 64 patients (placebo n = 33; glutamine n = 31) who completed RT for the completers’ analysis. Based on multivariate analysis, glutamine had no significant effect on the severity of oral mucositis (OR: 0.3; 95% CI: 0.05, 1.67; P = 0.169). Only the change in body mass index (BMI) was significant in both multivariate completers (OR: 0.41; 95% CI: 0.20, 0.84; P = 0.015) and per-protocol analysis (OR: 0.40; 95% CI: 0.20, 0.83; P = 0.014). No difference was found in the incidence and severity of neck dermatitis between the two arms.ConclusionsThe decrease in BMI was strongly related to the severity of oral mucositis in the head and neck cancer patients under RT, but not to the use of glutamine. This trial was registered at clinicaltrials.gov as NCT03015077.
20 show abstract
0002-9165 * 1938-3207 * 29607822

ABSTRACT
BackgroundAccurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake.ObjectivesThe goal of this study was to identify serum metabolites associated with dietary protein intake.MethodsMetabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography–tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25–55 mL · min−1 · 1.73 m−
2) and 192 participants in study B (glomerular filtration rate: 13–24 mL · min−1 · 1.73 m−
2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10−5.ResultsIn study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine.ConclusionsAmong patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease.This trial was registered at clinicaltrials.gov as NCT03202914.
21 show abstract
0002-9165 * 1938-3207 * 29607823

ABSTRACT
BackgroundAccurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake.ObjectivesThe goal of this study was to identify serum metabolites associated with dietary protein intake.MethodsMetabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography–tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25–55 mL · min−1 · 1.73 m−
2) and 192 participants in study B (glomerular filtration rate: 13–24 mL · min−1 · 1.73 m−
2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10−5.ResultsIn study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine.ConclusionsAmong patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease.This trial was registered at clinicaltrials.gov as NCT03202914.
22 show abstract
0002-9165 * 1938-3207 * 29607824

ABSTRACT
BackgroundA substantial portion of greenhouse gas emissions (GHGE) has been attributed to the food sector, but little is known about the association between the carbon footprint of individual self-selected diets in the United States and nutritional quality.ObjectivesThe aims of this study were to assess the GHGE from individual self-selected diets in the United States and examine their association with nutritional quality of the diets, demographic patterns, and food-related behaviors.MethodsThe dietary GHGE from US adults (>18 y, N = 16,800) in the 2005–2010 National Health and Nutrition Examination Survey (NHANES) were calculated by linking all foods consumed in their 24-h recall diets to our new database of food environmental impacts. Diets were ranked by GHGE/1000 kcal. Those in the top and bottom quintiles were compared on the US Healthy Eating Index (HEI) and on the amounts of specific nutrients known to be under- or overconsumed in the US population. Demographic and behavioral variables from the NHANES were also correlated to these dietary carbon footprints.ResultsDiets in the bottom quintile accounted for one-fifth the total emissions (GHGE/1000 kcal) of those in the top quintile, yet had significantly higher (P < 0.001) HEI scores by 2.3 ± 0.7 points on a 100-point scale. These low-GHGE diets contained higher amounts of fiber and vitamin E and lower amounts of sodium and saturated fats, whereas high-GHGE diets contained higher amounts of vitamins A and D, choline, calcium, iron, and potassium. Low-GHGE diets had less meat, dairy, and solid fats, and more poultry, plant protein foods, oils, whole and refined grains, and added sugars.ConclusionsFood patterns responsible for lower GHGE had a better overall diet quality and were more nutritious on several key dimensions, although not all. These results can inform dietary guidance and other policies that seek to address the goals of improved dietary intakes and reduced food-related emissions.
23 show abstract
0002-9165 * 1938-3207 * 29607825

ABSTRACT
BackgroundA growing amount of data suggests that n–3 (ω-3) polyunsaturated fatty acid (PUFA) intake may modify the genetic association with weight change.ObjectivesWe aimed to prospectively test interactions of habitual consumption of n–3 PUFAs or fish, the major food source, with overall genetic susceptibility on long-term weight change.DesignGene–diet interactions were examined in 11,330 women from the Nurses’ Health Study (NHS), 6773 men from the Health Professionals Follow-Up Study (HPFS), and 6254 women from the Women's Health Initiative (WHI).ResultsIn the NHS and HPFS cohorts, food-sourced long-chain n–3 PUFA intake showed directionally consistent interactions with genetic risk score on long-term changes in BMI (P-interaction = 0.01 in the HPFS, 0.15 in the NHS, and 0.01 in both cohorts combined). Such interactions were successfully replicated in the WHI, an independent cohort (P-interaction = 0.02 in the WHI and 0.01 in the combined 3 cohorts). The genetic associations with changes in BMI (in kg/m2) consistently decreased (0.15, 0.10, 0.07, and −0.14 per 10 BMI-increasing alleles) across the quartiles of long-chain n–3 PUFAs in the combined cohorts. In addition, high fish intake also attenuated the genetic associations with long-term changes in BMI in the HPFS (P-interaction = 0.01), NHS (P-interaction = 0.03), WHI (P-interaction = 0.10), and the combined cohorts (P-interaction = 0.01); and the differences in BMI changes per 10 BMI-increasing alleles were 0.16, 0.06, −0.08, and −0.18, respectively, across the categories (≤1, 1∼4, 4∼6, and ≥7 servings/wk) of total fish intake. Similar interactions on body weight were observed for fish intake (P-interaction = 0.003) and long-chain n–3 PUFA intake (P-interaction = 0.12).ConclusionOur study provides replicable evidence to show that high intakes of fish and long-chain n–3 PUFAs are associated with an attenuation of the genetic association with long-term weight gain based on results from 3 prospective cohorts of Caucasians.

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Journal Citation Reports (2017)

Impact factor: 6.549
Q1 (Nutrition & Dietetics (4/81))

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SJR: 3.438
SNIP: 2.191
Impact (Scopus CiteScore): 0.562
Quartile: Q1
CiteScore percentile: 96%
CiteScore rank: 4 out of 112
Cited by WUR staff: 1792 times. (2014-2016)

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