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Article URL: https://academic.oup.com/ajcn/article/110/6/1519/5645612?rss=1
Citation: Vol 110 No. 6 (2019) pp 1519 1519
Publication Date: Mon, 02 Dec 2019 00:00:00 GMT
Journal: American Journal of Clinical Nutrition

Article URL: https://academic.oup.com/ajcn/article/110/6/1514/5645610?rss=1
Citation: Vol 110 No. 6 (2019) pp 1514 1518
Publication Date: Mon, 02 Dec 2019 00:00:00 GMT
Journal: American Journal of Clinical Nutrition

Authors: Halpern B.
Article URL: https://academic.oup.com/ajcn/article/110/6/1513/5645609?rss=1
Citation: Vol 110 No. 6 (2019) pp 1513 1513
Publication Date: Mon, 02 Dec 2019 00:00:00 GMT
Journal: American Journal of Clinical Nutrition

Authors: Marlatt K ; Ravussin E.
Article URL: https://academic.oup.com/ajcn/article/110/6/1514/5645600?rss=1
Citation: Vol 110 No. 6 (2019) pp 1514 1514
Publication Date: Mon, 02 Dec 2019 00:00:00 GMT
Journal: American Journal of Clinical Nutrition

Authors: Ibsen D ; Jakobsen M ; Overvad K.
Article URL: https://academic.oup.com/ajcn/article/110/6/1510/5645598?rss=1
Citation: Vol 110 No. 6 (2019) pp 1510 1510
Publication Date: Mon, 02 Dec 2019 00:00:00 GMT
Journal: American Journal of Clinical Nutrition

Authors: Brouwer-Brolsma E ; Raben A ; Feskens E.
Article URL: https://academic.oup.com/ajcn/article/110/6/1512/5645595?rss=1
Citation: Vol 110 No. 6 (2019) pp 1512 1512
Publication Date: Mon, 02 Dec 2019 00:00:00 GMT
Journal: American Journal of Clinical Nutrition

Authors: Greenberg J.
Article URL: https://academic.oup.com/ajcn/article/110/6/1511/5645589?rss=1
Citation: Vol 110 No. 6 (2019) pp 1511 1511
Publication Date: Mon, 02 Dec 2019 00:00:00 GMT
Journal: American Journal of Clinical Nutrition

Simple measurements of body shape have long been used to assess nutritional status. Even BMI, which adjusts weight for height, represents a very crude index of relative volume, but provides no information on where body weight is anatomically distributed. Measuring body girths represents a first step to address this.

ABSTRACT
BackgroundExogenous ketones make it possible to reach a state of ketosis that may improve metabolic control in humans.ObjectivesThe main objective of this study was to determine whether the ingestion of a ketone monoester (KE) drink before a 2-h oral-glucose-tolerance test (OGTT) would lower blood glucose concentrations. Secondary objectives were to determine the impact of KE on nonesterified fatty acid (NEFA) concentration and glucoregulatory hormones.MethodsWe conducted a randomized controlled crossover experiment in 15 individuals with obesity (mean ± SD age: 47 ± 10 y; BMI: 34 ± 5 kg/m2). After an overnight fast, participants consumed a KE drink [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate; 0.45 mL/kg body weight] or taste-matched control drink 30 min before completing a 75-g OGTT. Participants and study personnel performing laboratory analyses were blinded to each condition.ResultsThe KE increased d-β-hydroxybutyrate to a maximum of ∼3.4 mM (P < 0.001) during the OGTT. Compared with the control drink, KE reduced glucose (−11%, P = 0.002), NEFA (−21%, P = 0.009), and glucagon-like peptide 1 (−31%, P = 0.001) areas under the curve (AUCs), whereas glucagon AUC increased (+11%, P = 0.030). No differences in triglyceride, C-peptide, and insulin AUCs were observed after the KE drink. Mean arterial blood pressure decreased and heart rate increased after the KE drink (both P < 0.01).ConclusionsA KE drink consumed before an OGTT lowered glucose and NEFA AUCs with no increase in circulating insulin. Our results suggest that a single drink of KE may acutely improve metabolic control in individuals with obesity. Future research is warranted to examine whether KE could be used safely to have longer-term effects on metabolic control. This trial was registered at clinicaltrials.gov as NCT03461068.

ABSTRACT
BackgroundFish oil improves cardiometabolic markers in adults, but results in children are inconsistent. Few children meet the recommended fish intake and no randomized trials have investigated how fish intake per se affects children's cardiometabolic profile.ObjectiveWe investigated whether oily fish consumption modulated serum triacylglycerol and diastolic blood pressure (coprimary outcomes) and other cardiometabolic markers in healthy Danish children and whether effects were sex-specific.MethodsIn a randomized controlled 12-wk trial, 199 children (aged 8–9 y) received ∼300 g/wk of oily fish or poultry (control). We measured blood pressure, heart rate, and heart rate variability (HRV) via 3-h continuous electrocardiograms and collected fasting blood samples for analysis of erythrocyte EPA [20:5n–3 (ω-3)] + DHA (22:6n–3) and serum triacylglycerol, LDL and HDL cholesterol, glucose, and insulin.ResultsOne hundred and ninety-seven children (99%) completed the trial. The fish group consumed a median (IQR) of 375 (325–426) g oily fish/wk and the poultry group consumed 400 (359–452) g poultry/wk, which resulted in 2.25 (95% CI: 1.88, 2.62) fatty acid percentage-point higher erythrocyte EPA + DHA in the fish group (P < 0.001). In the fish group, serum triacylglycerol decreased by 0.05 mmol/L (95% CI: 0.00, 0.11 mmol/L) (P = 0.04) and HDL cholesterol increased by 0.07 mmol/L (95% CI: 0.01, 0.13 mmol/L) (P = 0.02); the triacylglycerol effect showed dose-dependency with erythrocyte EPA + DHA (r = −0.15, P = 0.04), whereas HDL showed a tendency for such an association(r = 0.13, P = 0.08). Additional analyses indicated sex-specificity (P
diet*sex < 0.10), because triacylglycerol was reduced by 0.09 mmol/L (95% CI: 0.02, 0.16 mmol/L) in boys only (girls: −0.00; 95% CI: −0.07, 0.07 mmol/L) and heart rate was reduced by 3.4 bpm (95% CI: 0.2, 6.6 bpm) in girls only (boys: 0.6; 95% CI: −2.6, 3.8 bpm). Blood pressure, HRV, and glucose homeostasis were unaffected.ConclusionsOily fish intake improved serum triacylglycerol and HDL cholesterol in a dose-dependent manner in 8- to 9-y-old children, but had no effect on blood pressure, HRV, or glucose homeostasis. This supports recommendations for fish intake in children and underlines the importance of initiatives to increase children's intake of oily fish. This trial was registered at clinicaltrials.gov as NCT02809508.

ABSTRACT
BackgroundFatty acids are a vital component of human milk. They influence infant neurodevelopment and immune function, and they provide ∼50% of milk's energy content.ObjectivesThe objectives of this study were to characterize the composition of human milk fatty acids in a large Canadian birth cohort and identify factors influencing their variability.MethodsIn a subset of the CHILD cohort (n = 1094), we analyzed milk fatty acids at 3–4 mo postpartum using GLC. Individual and total SFAs, MUFAs, and n–3 and n–6 PUFAs were analyzed using SD scores and principal component analysis (PCA). Maternal diet, sociodemographic, health, and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in the fatty acid desaturase 1 (FADS1-rs174556) and 2 (FADS2-rs174575) genes.ResultsFatty acid profiles were variable, with individual fatty acid proportions varying from 2- to >30-fold between women. Using PCA, we identified 4 milk fatty acid patterns: “MUFA and low SFA,” “high n–6 PUFA,” “high n–3 PUFA,” and “high medium-chain fatty acids.” In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with DHA and the “high n–3 PUFA” pattern. Mothers carrying the minor allele of FADS1-rs174556 had lower proportions of arachidonic acid (ARA; 20:4n–6). Independent of selected dietary variables and genetic variants, Asian ethnicity was associated with higher linoleic acid (18:2n–6) and total n–3 PUFAs. Ethnic differences in ARA were explained by FADS1 genotype. Maternal obesity was independently associated with higher total SFAs, the “high medium-chain fatty acid” pattern, and lower total MUFAs. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, delivery mode, or infant sex.ConclusionsThis study provides unique insights about the “normal” variation in the composition of human milk fatty acids and the contributing dietary, genetic, sociodemographic, health, and environmental factors. Further research is required to assess implications for infant health.

ABSTRACT
BackgroundA highly soluble iron–casein complex has been developed for food fortification purposes with the aim to provide high iron bioavailability.ObjectiveWe aimed to determine the iron bioavailability of the iron–casein complex relative to that of ferrous sulfate (control) when given with whole milk in healthy young women.MethodsA randomized comparator-controlled trial with a crossover design was conducted using the erythrocyte incorporation dual stable isotope (57Fe, 58Fe) technique. Iron absorption from the iron–casein complex was compared with that from ferrous sulfate in 21 healthy women aged 20–38 y with normal iron status.ResultsFractional iron absorption (geometric mean; −SD, +SD) from the iron–casein complex (3.4%; 1.4%, 5.4%) and from ferrous sulfate (3.9%; 1.7%, 6.1%) were not statistically different (P > 0.05). The relative bioavailability value of the iron–casein complex to ferrous sulfate was determined to be 0.87 (−1 SD, +1 SD: −0.90, +2.64).ConclusionsThe iron–casein complex has iron bioavailability comparable to that of ferrous sulfate in healthy young women. This trial was registered at www.anzctr.org.au as ACTRN12615000690550.

ABSTRACT
BackgroundIn 2014, the World Food Programme added to an ongoing health and nutrition program named “Santé Nutritionnelle à Assise Communautaire dans la région de Kayes” (SNACK), the distribution of cash to mothers and/or lipid-based nutrient supplement (LNS) to children aged 6–23 mo, conditional upon attendance at community health centers (CHCs) during the first 1000 d of life.ObjectiveWe evaluated the additional impact of the distribution of cash and/or LNS on mean height-for-age z scores (HAZ; primary outcome), stunting (HAZ < −2), and on intermediate outcomes along the program impact pathways.MethodsIn a cluster-randomized controlled trial using a 2 × 2 factorial design, 76 CHCs were randomly assigned to deliver either SNACK, SNACK + Cash, SNACK + LNS, or SNACK + Cash + LNS. Cross-sectional surveys among 12- to 42-mo-old children and their mothers were conducted at baseline (2013, n = 5046) and at endline (2016, n = 5098).ResultsFactorial analysis showed no interaction between cash and LNS treatments for HAZ, but found an antagonistic interaction for stunting (OR: 1.55; 95% CI: 1.05, 2.31; P = 0.03). There were no impacts of the cash, LNS, or cash + LNS treatments, compared with the SNACK alone, on either HAZ or stunting (treatment × time interaction). There were significant impacts of the LNS and cash + LNS treatments on attendance at ≥1 growth monitoring (GM) session (OR: 3.95; 95% CI: 1.69, 9.24; OR: 3.90; 95% CI: 1.73, 8.81, respectively) and half the expected sessions (OR: 4.72; 95% CI: 1.47, 15.17; OR: 5.25; 95% CI: 1.82, 15.11, respectively), mothers’ knowledge on importance of GM (OR: 1.98; 95% CI: 1.16, 3.39; OR: 3.12; 95% CI: 1.60, 6.09, respectively), and, only for the LNS group, appropriate timing for complementary feeding (OR: 1.62; 95% CI: 1.09, 2.41).ConclusionsImplementation constraints and suboptimal participation in program activities may explain the lack of impact on child linear growth in this rural region of Mali.This trial was registered at www.isrctn.com as ISRCTN08435964.

ABSTRACT
BackgroundEpidemiological studies in humans show increased concentrations of copeptin, a surrogate marker of arginine vasopressin (AVP), to be associated with increased risk for type 2 diabetes.ObjectivesTo examine the acute and independent effect of osmotically stimulated AVP, measured via the surrogate marker copeptin, on glucose regulation in healthy adults.MethodsSixty subjects (30 females) participated in this crossover design study. On 2 trial days, separated by ≥7 d (males) or 1 menstrual cycle (females), subjects were infused for 120 min with either 0.9% NaCl [isotonic (ISO)] or 3.0% NaCl [hypertonic (HYPER)]. Postinfusion, a 240-min oral-glucose-tolerance test (OGTT; 75 g) was administered.ResultsDuring HYPER, plasma osmolality and copeptin increased (P < 0.05) and remained elevated during the entire 6-h protocol, whereas renin-angiotensin-aldosterone system hormones were within the lower normal physiological range at the beginning of the protocol and declined following infusion. Fasting plasma glucose did not differ between trials (P > 0.05) at baseline and during the 120 min of infusion. During the OGTT the incremental AUC for glucose from postinfusion baseline (positive integer) was greater during HYPER (401.5 ± 190.5 mmol/L·min) compared with the ISO trial (354.0 ± 205.8 mmol/L·min; P < 0.05). The positive integer of the AUC for insulin during OGTT did not differ between trials (HYPER 55,850 ± 36,488 pmol/L·min compared with ISO 57,205 ± 31,119 pmol/L·min). Baseline values of serum glucagon were not different between the 2 trials; however, the AUC of glucagon during the OGTT was also significantly greater in HYPER (19,303 ± 3939 ng/L·min) compared with the ISO trial (18,600 ± 3755 ng/L·min; P < 0.05).ConclusionsThe present data indicate that acute osmotic stimulation of copeptin induced greater hyperglycemic responses during the oral glucose challenge, possibly due to greater glucagon concentrations.This study was registered at clinicaltrials.gov as NCT02761434.

ABSTRACT
BackgroundProcessed meat intake is associated with a higher risk of colorectal and stomach cancers, coronary artery disease, and type 2 diabetes and with higher mortality, but the estimation of intake of different processed meat products in this heterogeneous food group in epidemiological studies remains challenging.ObjectiveThis work aimed at identifying novel biomarkers for processed meat intake using metabolomics.MethodsAn untargeted, multi-tiered metabolomics approach based on LC-MS was applied to 33 meat products digested in vitro and secondly to urine and plasma samples from a randomized crossover dietary intervention in which 12 volunteers consumed successively 3 processed meat products (bacon, salami, and hot dog) and 2 other foods used as controls, over 3 consecutive days. The putative biomarkers were then measured in urine from 474 subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study for which detailed 24-h dietary recalls and FFQs were available.ResultsSyringol and 4 derivatives of syringol were found to be characteristic of in vitro digests of smoked meat products. The same compounds present as sulfate esters in urine increased at 2 and 12 h after consumption of smoked meat products (hot dog, bacon) in the intervention study. The same syringol sulfates were also positively associated with recent or habitual consumption of smoked meat products in urine samples from participants of the EPIC cross-sectional study. These compounds showed good discriminative ability for smoked meat intake with receiver operator characteristic areas under the curve ranging from 0.78 to 0.86 and 0.74 to 0.79 for short-term and habitual intake, respectively.ConclusionsFour novel syringol sulfates were identified as potential biomarkers of smoked meat intake and may be used to improve assessment of smoked meat intake in epidemiological studies. This trial was registered at clinicaltrials.gov as NCT03354130.

ABSTRACT
BackgroundThree-dimensional optical (3DO) body scanning has been proposed for automatic anthropometry. However, conventional measurements fail to capture detailed body shape. More sophisticated shape features could better indicate health status.ObjectivesThe objectives were to predict DXA total and regional body composition, serum lipid and diabetes markers, and functional strength from 3DO body scans using statistical shape modeling.MethodsHealthy adults underwent whole-body 3DO and DXA scans, blood tests, and strength assessments in the Shape Up! Adults cross-sectional observational study. Principal component analysis was performed on registered 3DO scans. Stepwise linear regressions were performed to estimate body composition, serum biomarkers, and strength using 3DO principal components (PCs). 3DO model accuracy was compared with simple anthropometric models and precision was compared with DXA.ResultsThis analysis included 407 subjects. Eleven PCs for each sex captured 95% of body shape variance. 3DO body composition accuracy to DXA was: fat mass R
2 = 0.88 male, 0.93 female; visceral fat mass R
2 = 0.67 male, 0.75 female. 3DO body fat test-retest precision was: root mean squared error = 0.81 kg male, 0.66 kg female. 3DO visceral fat was as precise (%CV = 7.4 for males, 6.8 for females) as DXA (%CV = 6.8 for males, 7.4 for females). Multiple 3DO PCs were significantly correlated with serum HDL cholesterol, triglycerides, glucose, insulin, and HOMA-IR, independent of simple anthropometrics. 3DO PCs improved prediction of isometric knee strength (combined model R
2 = 0.67 male, 0.59 female; anthropometrics-only model R
2 = 0.34 male, 0.24 female).Conclusions3DO body shape PCs predict body composition with good accuracy and precision comparable to existing methods. 3DO PCs improve prediction of serum lipid and diabetes markers, and functional strength measurements. The safety and accessibility of 3DO scanning make it appropriate for monitoring individual body composition, and metabolic health and functional strength in epidemiological settings.This trial was registered at clinicaltrials.gov as NCT03637855.

Reliable dietary assessment methods are crucial for nutrition research. Without reliable information on intake, it is impossible to investigate effects on health, explore intake at population level, or develop dietary recommendations. Despite this importance, there is a paucity of such methods. Many studies still rely on self-reported dietary intake, despite the well-known limitations of these methods, especially to assess long-term habitual diet (1). These are, in particular, underreporting of energy (2) and sugar intake (3), but also the high variability in food composition (4).

This editorial refers to “Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial,” by Keith et al. (1) in this issue of the Journal.

Adequate nutrition is essential for maintenance of cognitive function during aging, and poor nutrition is one of the risk factors for developing mild cognitive impairment and progression to dementia (1, 2). Unlike current pharmacological agents, nutritional approaches have the potential to positively affect neurodegenerative processes well before manifestation of dementia (2). On the other hand, perhaps the most serious limitation to nutritional interventions is that participants are rarely naïve to the intervention, thus making it less likely that increased nutrient exposure will result in improved performance. In contrast, in the setting of chronic nutrient deficiencies, irreversible damage may have occurred (3).

ABSTRACT
BackgroundEmerging data suggest that weight gain is associated with changes in neural response to palatable food tastes and palatable food cues, which may serve to maintain overeating.ObjectiveWe investigated whether weight gain is associated with neural changes in response to tastes of milkshakes varying in fat and sugar content and palatable food images.MethodsWe compared changes in neural activity between initially healthy-weight adolescents who gained weight (n = 36) and those showing weight stability (n = 31) over 2–3 y.ResultsAdolescents who gained weight compared with those who remained weight stable showed decreases in activation in the postcentral gyrus, prefrontal cortex, insula, and anterior cingulate cortex, and increases in activation in the parietal lobe, posterior cingulate cortex, and inferior frontal gyrus in response to a high-fat/low-sugar compared with low-fat/low-sugar milkshake. Weight gainers also showed greater decreases in activation in the anterior insula and lateral orbitofrontal cortex in response to a high-fat/high-sugar compared with low-fat/low-sugar milkshake than those who remained weight stable. No group differences emerged in response to a low-fat/high-sugar compared with a low-fat/low-sugar milkshake. Weight gainers compared with those who remained weight stable showed greater decreases in activation in the middle temporal gyrus and increases in cuneus activation in response to appetizing compared with unappetizing food pictures. The significant interactions were partially driven by group differences in baseline responsivity and by opposite changes in neural activation in adolescents who remained weight stable.ConclusionsData suggest that weight gain is associated with a decrease in responsivity of regions associated with taste and reward processing to palatable high-fat- and high-fat/high-sugar food tastes. Data also suggest that avoiding weight gain increases taste sensitivity, which may prevent future excessive weight gain.This trial was registered at clinicaltrials.gov as NCT01949636.

ABSTRACT
BackgroundComparative studies suggest that DHA may have stronger serum triglyceride–lowering effects than EPA; however, the molecular basis for this differential effect remains unexplored in humans. Differential regulation of lipogenesis and triglyceride clearance are 2 possible mechanisms of action.ObjectivesWe compared the effects of EPA and DHA supplementation on serum triglycerides, markers of lipogenesis, and lipoprotein lipase (LPL) activity in adults participating in a double-blind, multiarm, placebo-controlled parallel-group randomized trial. Lipogenesis was assessed with the lipogenic index and compound specific isotope analysis (CSIA).MethodsYoung, healthy normolipidemic men and women (n = 89; 21.6 ± 0.23 y; mean ± SEM) were randomly allocated into 1 of 3 supplement groups for 12 wk: 1) olive oil, 2) ∼3 g EPA/d, and 3) ∼3 g DHA/d. Omega-3 supplements were provided in triglyceride form. Blood was collected before and after supplementation for the analysis of fatty acids and preheparin LPL activity. Variations in the 13C:12C ratio (δ13C) of palmitate (16:0) and linoleate (18:2n–6) were measured by CSIA.ResultsDHA supplementation reduced blood triglycerides (0.85 ± 0.04 mmol/L to 0.65 ± 0.03 mmol/L; P < 0.01), with no change seen with EPA supplementation. DHA supplementation did not change the lipogenic index or δ13C-16:0, whereas EPA supplementation increased the lipogenic index by 11% (P < 0.01) and δ13C-16:0 (P = 0.03) from −23.2 ± 0.2 to −22.8 ± 0.2 milliUrey ± SEM.ConclusionsReduced triglyceride concentrations after DHA supplementation are associated with increased LPL activity, whereas the null effect of EPA supplementation on blood triglycerides may stem from the concomitant increases in lipogenesis and LPL activity. Further investigation of the differential triglyceride-lowering effects of EPA and DHA is warranted in both normolipidemic and hyperlipidemic individuals. This trial was registered at clinicaltrials.gov as NCT03378232.

ABSTRACT
BackgroundData on how baseline characteristics, acuity, morbidity, and nutrition work in combination to affect the growth of very-low-birth-weight (VLBW, <1500 g) infants are limited.ObjectiveWe aimed to determine factors associated with in-hospital weight, length, and head circumference (HC) trajectories of VLBW infants.MethodsVLBW infants (n = 316) from the GTA-DoMINO trial were included. Linear mixed-effects models assessed relations of baseline characteristics, acuity (at birth, across hospitalization), major morbidities, and nutrition (enteral feeding type, macronutrient/energy intakes) with changes in anthropometrics over hospitalization (days 1–8, 9–29, 30–75).ResultsSpecific factors and the strength of their associations with growth depended on in-hospital time interval. Small-for-gestational-age infants experienced weight gain (4.3   g · kg−1 · d−1; 95% CI: 2.0, 6.5   g · kg−1 · d−1) during days 1–8, versus weight loss (−4.6     g · kg−1 · d−1; 95% CI: −5.6, −3.7     g · kg−1 · d−1) among appropriate-for-gestational-age infants (P < 0.001). Positive-pressure ventilation (versus oxygen/room air) was associated with slower weight (−1.8    g · kg−1 · d−1) and HC (−0.25 cm/wk) gain during days 9–29 (P < 0.001). Morbidities were negatively associated with growth after days 1–8, with patent ductus arteriosus (PDA) showing negative associations with weight (−2.7     g · kg−1 · d−1), length (−0.11 cm/wk), and HC (−0.21 cm/wk) gain during days 9–29 (P < 0.001). Macronutrient/energy intakes were associated with weight across hospitalization (P ≤ 0.01), with greater weight gain (1.3–3.0 g  ·  kg−1  ·  d−1) among infants achieving macronutrient/energy recommendations during days 9–29 and 30–75. Macronutrient/energy intakes were associated with HC during the first month (P = 0.013–0.003), with greater HC gain (0.07–0.12 cm/wk) among infants achieving protein, lipid, and energy recommendations during days 9–29.ConclusionsBaseline characteristics, acuity, morbidity, and nutrition factors were independently associated with VLBW infant growth. A focus on achieving macronutrient/energy recommendations and improving nutrient delivery to PDA-diagnosed infants may yield improvements to their growth. This trial was registered at www.isrctn.com as ISRCTN35317141.

ABSTRACT
BackgroundIn Mexico, wheat and corn flour fortification with folic acid (FA) was implemented in 2001 and mandated in 2008, but without direct enforcement. Current Mexican nutrient-content tables do not account for FA contained in bakery bread and corn masa–based foods, which are dietary staples in Mexico.ObjectiveThe objective of this study was to examine the impact of FA fortification of dietary staples on the proportion of the population consuming below the Estimated Average Requirement (EAR) for folate or above the Tolerable Upper Intake Level (UL) for FA.MethodsWe measured FA and folate content in dietary staples (bakery bread and tortillas) using microbial assays and MS, and we recalculated FA intake from 24-h recall dietary intake data collected in the 2012 Mexican National Health and Nutrition Survey (Encuesta Nacional de Salud y Nutrición) utilizing estimates from our food measurements, using nutrient concentrations from tortillas to approximate nutrient content of other corn masa–derived foods. The revised FA intake estimates were used to examine population-level intake of FA and dietary folate equivalent (DFE) accounting for geographic differences in FA content with statistical models.ResultsFA content in dietary staples was variable, whereas use of FA-fortified flour in corn masa tortillas increased with population size in place of residence. Accounting for dietary staples’ FA fortification increased population estimates for FA and DFE intake, resulting in a lower proportion with intake below the EAR and a higher proportion with intake above the UL. Despite accounting for FA-fortified staple foods, 9–33% of women of childbearing age still have intake below the EAR, whereas up to 12% of younger children have intake above the UL.ConclusionsUnregulated FA fortification of dietary staples leads to unpredictable total folate intake without adequately impacting the intended target. Our findings suggest that monitoring, evaluation, and enforcement of mandatory fortification policies are needed. Without these, alternate strategies may be needed in order to reach women of childbearing age while avoiding overexposing children.

ABSTRACT
BackgroundNutritional status is an important factor affecting a patient's clinical outcomes. Early identification of patients who are at risk of malnutrition is important to improve clinical outcomes and reduce health cost. The Malnutrition Universal Screening Tool (MUST) has been recommended as part of the routine nursing assessment for all patients at hospital admission.ObjectiveThe aim of this study was to examine the association between nutritional status (MUST), systemic inflammatory response (SIR), body composition, and clinical outcomes in patients undergoing surgery for colorectal cancer.MethodsThe malnutrition risk was examined using MUST in patients admitted for surgery for colorectal cancer between March 2013 and June 2016. Preoperative computed tomography scans were used to define the body composition. The presence of SIR was evidenced by the modified Glasgow prognostic score and the neutrophil to lymphocyte ratio. Postoperative complications, severity of complication, length of hospital stay, and mortality were considered as outcome measures.ResultsThe study included 363 patients (199 males, 164 females); 21% of the patients presented with a medium or high nutritional risk. There were significant associations between MUST and subcutaneous adiposity (P < 0.001), visceral obesity (P < 0.001), and low skeletal muscle index (P < 0.001). No statistically significant association was identified between MUST score and presence of any complication or severity of complication. On multivariate analysis, MUST remained independently associated with the length of hospital stay (OR: 2.17; 95% CI: 1.45, 3.26; P < 0.001). Kaplan–Meier survival curves showed an increased number of deaths for patients at medium or high risk of malnutrition (P < 0.001). This association was found to be independent of other confounding factors (HR: 1.45; 95% CI: 1.06, 1.99; P = 0.020).ConclusionsMUST score is an independent marker of risk in those undergoing surgery for colorectal cancer and should remain a key part of preoperative assessment.

ABSTRACT
BackgroundVitamin K has multiple important physiological roles, including blood coagulation and beneficial effects on myelin integrity in the brain. Some intestinal microbes possess the genes to produce vitamin K in the form of menaquinone (MK). MK appears in higher concentration in tissues, such as the brain, particularly MK4, than the dietary form of phylloquinone (PK). Lower PK concentrations have been reported in patients with Alzheimer disease while higher serum PK concentrations have been positively associated with verbal episodic memory. Despite knowledge of the importance of vitamin K for various health parameters, few studies have measured MK concentration and biosynthesis by gut commensals.ObjectiveThe aim of the current study was to investigate the relation between genes involved in gut-microbiota derived MK, concentrations of MK isoforms, and cognitive function.MethodsShotgun metagenomic sequencing of the gut microbiome of 74 elderly individuals with different cognitive ability levels was performed. From this, gene counts for microbial MK biosynthesis were determined. Associations between clusters of individuals, grouped based on a similar presence and prevalence of MK biosynthesis genes, and cognitive ability were investigated. Fecal MK concentrations were quantified by HPLC to investigate correlations with subject clusters.ResultsSeparation of subject groups defined by banded quantification of the genetic potential of their microbiome to biosynthesize MK was associated with significant differences in cognitive ability [assessed using the Mini-Mental State Examination (MMSE)]. Three MK isoforms were found to be positively associated with MMSE, along with the identification of key components of the MK pathway that drive this association. Although the causality and direction of these associations remain unknown, these findings justify further studies.ConclusionsThis study provides evidence that although total concentrations of MK did not covary with cognition, certain MK isoforms synthesized by the gut microbiome, particularly the longer chains, are positively associated with cognition.

ABSTRACT
BackgroundThe minerals, vitamins, soluble dietary fibers, and flavonoids of seaweed are protective for preventing cardiovascular diseases. However, the association between seaweed intake and risk of cardiovascular disease has not been established.ObjectivesWe examined the dietary intake of seaweed and its impact upon stroke and ischemic heart disease risk among a Japanese study population.MethodsWe surveyed 40,707 men and 45,406 women from 2 large cohorts (age range: 40–69 y). Seaweed intake was determined by FFQ at baseline (1990–1994). Incidences of stroke and ischemic heart disease were ascertained until the end of 2009 (Cohort I) or 2012 (Cohort II). Sex-specific cardiovascular disease HRs (95% CIs) were estimated using Cox proportional hazard models after stratification by area and adjustment for cardiovascular disease risk and dietary factors.ResultsDuring 1,493,232 person-years of follow-up, 4777 strokes (2863 ischemic stroke, 1361 intraparenchymal hemorrhages, and 531 subarachnoid hemorrhages) and 1204 ischemic heart disease cases were identified. Among men, significant multivariable HRs (95% CIs) for almost daily consumption compared with almost no consumption of seaweed were seen in ischemic heart disease [0.76 (0.58, 0.99); P-trend = 0.04] and total cardiovascular diseases [0.88 (0.78, 1.00); P-trend = 0.08]. Among women, such inverse associations were 0.56 (0.36, 0.85; P-trend = 0.006) for ischemic heart disease and 0.89 (0.76, 1.05; P-trend = 0.10) for total cardiovascular diseases. No significant associations were observed between seaweed intake and risk of total stroke or stroke types among either men or women.ConclusionsSeaweed intake was inversely associated with risk of ischemic heart disease.

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BackgroundNaturally occurring carbon and nitrogen stable isotope ratios [13C/12C (CIR) and 15N/14N (NIR)] are promising dietary biomarkers. As these candidate biomarkers have long tissue residence times, long-term feeding studies are needed for their evaluation.ObjectiveOur aim was to evaluate plasma, RBCs, and hair CIR and NIR as biomarkers of fish, meat, and sugar-sweetened beverage (SSB) intake in a 12-wk dietary intervention.MethodsThirty-two men (aged 46.2 ± 10.5 y; BMI: 27.2 ± 4.0 kg/m2) underwent a 12-wk inpatient dietary intervention at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in Phoenix, Arizona. The effects of fish, meat, and SSB intake on CIR and NIR were evaluated using a balanced factorial design, with each intake factor at 2 levels (present/absent) in a common, background diet (50% carbohydrate, 30% fat, 20% protein). Fasting blood samples were taken biweekly from baseline, and hair samples were collected at baseline and postintervention. Data were analyzed using multivariable regression.ResultsThe postintervention CIR of plasma was elevated when diets included meat (β = 0.89, 95% CI: 0.73,1.05) and SSBs (β = 0.48, 95% CI: 0.32, 0.64). The postintervention NIR of plasma was elevated when diets included fish (β = 0.85, 95% CI: 0.64, 1.05) and meat (β = 0.61, 95% CI: 0.42, 0.8). Results were similar for RBCs and hair. Postintervention RBC CIR and NIR had strong associations with baseline, suggesting that turnover to the intervention diets was incomplete after 12 wk. Estimates of isotopic turnover rate further confirmed incomplete turnover of RBCs.ConclusionsCIR was associated with meat and SSBs, and more strongly with meat. NIR was associated with fish and meat, and more strongly with fish. Overall, CIR and NIR discriminated between dietary fish and meat, and to a lesser extent SSBs, indicating their potential utility as biomarkers of intake in US diets. Approaches to make these biomarkers more specific are needed. This trial was registered at clinicaltrials.gov as NCT01237093.

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BackgroundKnowledge of the evolution of BMI and skeletal muscle index (SMI) measurements during advanced cancer and their relationships with disease progression (PD) is relevant to improve the timing of interventions that may improve cachexia-associated outcomes.ObjectivesWe investigated BMI and SMI trajectories and their associations with PD in metastatic colorectal cancer (mCRC) patients during consecutive palliative systemic regimens.MethodsIn a secondary analysis of the primary CAIRO3 trial, we included 533 mCRC patients with BMI measurements repeated every 3 wk and 95 randomly selected patients with SMI measurements repeated every 9 wk. We studied 2 periods: p1, during first-line maintenance capecitabine + bevacizumab or observation until the first progression of disease (PD1); and p2, during capecitabine + oxaliplatin + bevacizumab or another reintroduction treatment from PD1 until the second progression of disease (PD2). BMI and SMI trajectories were modeled separately throughout both periods, and joint longitudinal-survival modeling was used to investigate the relationships between slopes in BMI and SMI with PD at 9 and 3 wk pre-PD. A multivariate longitudinal joint model was used to investigate the association between the BMI trajectory and PD at time of PD, independent of SMI.ResultsDuring p1, the slopes in BMI and SMI were associated with early PD1 [HRs for 9-wk BMI: 1.54 (95% CI: 1.33, 1.76); 9-wk SMI: 1.38 (95% CI: 0.87, 1.89), NS; 3-wk BMI: 1.74 (95% CI: 1.48, 1.99); 3-wk SMI: 2.65 (95% CI: 1.97, 3.32)]. During p2, only the slope in SMI was related to PD2 [9-wk BMI: 1.09 (95%: CI: 0.73, 1.45), NS; 9-wk SMI: 1.64 (95% CI: 1.25, 2.04); 3-wk BMI: 1.17 (95% CI: 0.77, 1.57); 3-wk SMI: 1.11 (95% CI: 0.70, 1.53)]. In models mutually adjusting for BMI and SMI, SMI was associated with PD in p1 [p1 ( n = 95), HR BMI: 1.32 (95% CI: 0.74, 2.39), NS; p1, HR SMI: 1.50 (95% CI: 1.04, 2.14); p2 ( n = 50), BMI: 0.98 (95% CI: 0.55, 1.75), NS; p2, HR SMI: 1.11 (95% CI: 0.61, 2.05), NS].ConclusionsIn mCRC patients during palliative systemic treatment, SMI losses, irrespective of BMI losses, may be a marker for the early initiation of cachexia interventions.

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BackgroundDietary phytate inhibits zinc absorption from composite meals in adults.ObjectiveThe objective of this study was to investigate the effect of adding exogenous phytase to a small-quantity lipid-based nutrient supplement (SQ-LNS) on zinc absorption among young children.MethodsIn a double-blind randomized controlled trial, intraindividual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from a millet-based porridge containing SQ-LNS with and without phytase were measured in 30 asymptomatic children 18–23 mo of age in the Kiang West district of The Gambia. Using a crossover design, children received for 1 d each porridge test meals with 20 g SQ-LNS containing 8 mg zinc and either 1) exogenous phytase or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a triple stable isotope tracer ratio technique with Zn-67 and Zn-70 as oral tracers and Zn-68 as the intravenous tracer.ResultsTwenty-six participants completed the study. The prevalence of stunting and wasting were 20% and 13%, respectively; no children had low plasma zinc concentrations (<65 μg/dL). Total mean ± SD dietary zinc intake from the test meals was 7.3 ± 2.2 mg (phytate:zinc molar ratio = 3.1 ± 0.3, not accounting for phytase activity). Mean FAZ increased from 8.6% ± 1.3% to 16.0% ± 1.3% when exogenous phytase was added to the SQ-LNS product (P < 0.001). Mean TAZ from test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.1 ± 0.1 mg and 0.5 ± 0.1 mg, respectively; P < 0.001).ConclusionsThe addition of exogenous phytase to SQ-LNS increased both FAZ and TAZ. These results suggest that phytate reduction may be an important strategy to increase zinc absorption among young children. This trial was registered at clinicaltrials.gov as NCT02668133.

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BackgroundHuman milk oligosaccharides (HMOs) were recently found in serum of normal-weight pregnant women, with concentrations increasing from early to mid- and late pregnancy. Whether HMOs have effects on maternal metabolism is unknown.ObjectivesWe aimed to study the presence and changes in HMOs throughout pregnancy and assess associations with maternal glucose metabolism throughout pregnancy.MethodsThe study was a prospective longitudinal cohort study including 87 overweight or obese women. Blood samples were taken at 15, 24, and 32 wk of pregnancy. In serum, 4 HMOs [2′-fucosyllactose (2′FL), lactodifucotetraose (LDFT), 3′-sialyllactose (3′SL), and 3′-sialyllactosamine (3′SLN)] were measured. In linear regression models, the associations between HMOs and (changes in) maternal metabolic parameters were assessed.ResultsAll 4 HMOs showed a significant increase from 15 to 32 weeks of gestation. 3′SL and 3′SLN, but not 2′FL or LDFT, at 15 wk were positively associated with (changes in) fasting glucose at 24 and 32 wk. LDFT was positively associated with (changes in) insulin and HOMA-index at 24 but not 32 wk. A model to predict the development of gestational diabetes mellitus (GDM) that included fasting glucose, prepregnancy BMI, gestational weight gain, age, parity, smoking, and history of macrosomia resulted in an area under the curve (AUC) of 0.81 (95% CI: 0.70, 0.92). Adding 3′SL to this model increased the AUC to 0.91 (95% CI: 0.84, 0.97).ConclusionsThe sialylated HMOs 3′SL and 3′SLN were associated with fasting glucose; LDFT was associated with fasting insulin and HOMA-index. Furthermore, 3′SL was more predictive of future GDM diagnoses than was fasting glucose in early pregnancy. Causal relations are unclear and need further investigation.

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BackgroundTo accurately assess micronutrient status, it is necessary to characterize the effects of inflammation and the acute-phase response on nutrient biomarkers.ObjectiveWithin a norovirus human challenge study, we aimed to model the inflammatory response of C-reactive protein (CRP) and α-1-acid glycoprotein (AGP) by infection status, model kinetics of micronutrient biomarkers by inflammation status, and evaluate associations between inflammation and micronutrient biomarkers from 0 to 35 d post–norovirus exposure.MethodsFifty-two healthy adults were enrolled into challenge studies in a hospital setting and followed longitudinally; all were exposed to norovirus, half were infected. Post hoc analysis of inflammatory and nutritional biomarkers was performed. Subjects were stratified by inflammation resulting from norovirus exposure. Smoothed regression models analyzed the kinetics of CRP and AGP by infection status, and nutritional biomarkers by inflammation. Linear mixed-effects models were used to analyze the independent relations between CRP, AGP, and biomarkers for iron, vitamin A, vitamin D, vitamin B-12, and folate from 0 to 35 d post–norovirus exposure.ResultsNorovirus-infected subjects had median (IQR) peak concentrations for CRP [16.0 (7.9–29.5) mg/L] and AGP [0.9 (0.8–1.2) g/L] on day 3 and day 4 postexposure, respectively. Nutritional biomarkers that differed (P < 0.05) from baseline within the inflamed group were ferritin (elevated day 3), hepcidin (elevated days 2, 3), serum iron (depressed days 2–4), transferrin saturation (depressed days 2–4), and retinol (depressed days 3, 4, and 7). Nutritional biomarker concentrations did not differ over time within the uninflamed group. In mixed models, CRP was associated with ferritin (positive) and serum iron and retinol (negative, P < 0.05).ConclusionUsing an experimental infectious challenge model in healthy adults, norovirus infection elicited a time-limited inflammatory response associated with altered serum concentrations of certain iron and vitamin A biomarkers, confirming the need to consider adjustments of these biomarkers to account for inflammation when assessing nutritional status. These trials were registered at clinicaltrials.gov as NCT00313404 and NCT00674336.

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BackgroundContemporary energy expenditure data are crucial to inform and guide nutrition policy in older adults to optimize nutrition and health.ObjectiveThe aim was to determine the optimal method of estimating total energy expenditure (TEE) in adults (aged ≥65 y) through 1) establishing which published predictive equations have the closest agreement between measured resting metabolic rate (RMR) and predicted RMR and 2) utilizing the RMR equations with the best agreement to predict TEE against the reference method of doubly labeled water (DLW).MethodsA database consisting of international participant-level TEE data from DLW studies was developed to enable comparison with energy requirements estimated by 17 commonly used predictive equations. This database included 31 studies comprising 988 participant-level RMR data and 1488 participant-level TEE data. Mean physical activity level (PAL) was determined for men (PAL = 1.69, n = 320) and women (PAL = 1.66, n = 668). Bland–Altman plots assessed agreement of measured RMR and TEE with predicted RMR and TEE in adults aged ≥65 y, and subgroups of 65–79 y and ≥80 y. Linear regression assessed proportional bias.ResultsThe Ikeda, Livingston, and Mifflin equations most closely agreed with measured RMR and TEE in all adults aged ≥65 y and in the 65–79 y and ≥80 y subgroups. In adults aged ≥65 y, the Ikeda and Livingston equations overestimated TEE by a mean ± SD of 175 ± 1362 kJ/d and 86 ± 1344 kJ/d, respectively. The Mifflin equation underestimated TEE by a mean ± SD of 24 ± 1401 kJ/d. Proportional bias was present as energy expenditure increased.ConclusionsThe Ikeda, Livingston, or Mifflin equations are recommended for estimating energy requirements of older adults. Future research should focus on developing predictive equations to meet the requirements of the older population with consideration given to body composition and functional measures.

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BackgroundThiamin, a water-soluble B-complex vitamin, functions as a coenzyme in macronutrient oxidation and in the production of cellular ATP. Data suggest that thiamin depletion occurs in heart failure (HF). Therefore, thiamin supplementation in HF patients may improve cardiac function.ObjectiveWe sought to determine whether oral thiamin supplementation improves left ventricular ejection fraction (LVEF), exercise tolerance, and quality of life among patients with HF and reduced LVEF.MethodsIn this prospective, multicenter, double-blind, placebo-controlled randomized trial, eligible ambulatory patients with HF and reduced LVEF were recruited from 4 academic and community hospitals between 2010 and 2015. Participants were randomly assigned to receive either 200 mg oral thiamin mononitrate per day or placebo for 6 mo.ResultsSixty-nine patients (mean ± SD age: 64 ± 12 y; 83% men; LVEF: 37% ± 11%) were randomly assigned: 34 received placebo and 35 received thiamin supplementation. Erythrocyte thiamin pyrophosphate and urine thiamin concentrations were significantly higher in the supplemented group than in the placebo group at 6 mo (P = 0.02 and <0.001, respectively). At 6 mo, LVEF was significantly higher in the placebo group than in the thiamin group (38%; 95% CI: 36%, 39% compared with 35%; 95% CI: 33%, 37%, P = 0.047) after adjusting for baseline measurements. There were no significant differences in Minnesota Living with Heart Failure score, distance walked in 6 min, and N-terminal prohormone of brain natriuretic peptide concentrations between the 2 groups. One patient (2.9%) in the thiamin-supplemented group and none in the control group died at 6 mo.ConclusionsIn ambulatory patients with HF and reduced LVEF, thiamin supplementation for 6 mo did not improve LVEF, quality of life, or exercise capacity, despite increases in thiamin concentrations. These findings do not support routine thiamin supplementation in the treatment of HF and reduced LVEF.This trial was registered at clinicaltrials.gov as NCT00959075.

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BackgroundModerate egg intake has been associated with better cognitive performance in observational studies. This association may be due to the rich content of choline, especially phosphatidylcholine, in eggs because choline has been suggested to have a role in the prevention of cognitive decline.ObjectivesWe investigated the associations of dietary choline intake with the risk of incident dementia and with cognitive performance in middle-aged and older men in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study.MethodsA population-based sample of 2497 dementia-free men aged 42–60 y was examined in 1984–1989. A subset of 482 men completed 5 different cognitive performance tests 4 y later. Dementia and Alzheimer disease diagnoses were retrieved from Finnish health registers. Dietary intakes were assessed with the use of 4-d food records at baseline. Cox regression and ANCOVA were used for the analyses. All analyses were also stratified by the apolipoprotein E phenotype (APOE-ε4 compared with other phenotypes). These data were available for 1259 men.ResultsThe mean ± SD total choline intake was 431 ± 88 mg/d, of which 188 ± 63 mg/d was phosphatidylcholine. During a 21.9-y follow-up, 337 men were diagnosed with dementia. Those in the highest compared with the lowest phosphatidylcholine intake quartile had 28% (95% CI: 1%, 48%; P-trend = 0.02 across quartiles) lower multivariable-adjusted risk of incident dementia. Total choline intake had no association with the risk of incident dementia. However, both total choline and phosphatidylcholine intakes were associated with better performance in cognitive tests assessing frontal and temporal lobe functioning. For example, higher intakes were associated with better performance in verbal fluency and memory functions. The APOE phenotype had little or no impact on the associations.ConclusionHigher phosphatidylcholine intake was associated with lower risk of incident dementia and better cognitive performance in men in eastern Finland. This trial was registered at clinicaltrials.gov as NCT03221127.