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Background Optimal nutrition therapy has not yet been established for the acute phase of severe coronavirus disease 2019 (COVID-19) infection. Objectives We aimed to examine the effects of nutrition delivery in the acute phase on mortality and the long-term outcomes of post-intensive care syndrome (PICS). Methods A multicenter prospective study was conducted on adult patients with COVID-19 infection requiring mechanical ventilation during an intensive care unit (ICU) stay. Daily total energy (kcal/kg) and protein (g/kg) deliveries in the first week of the ICU stay were calculated. The questionnaire for PICS evaluation was mailed within a median of 6 mo after hospital discharge. The primary outcome was in-hospital mortality, and secondary outcomes were the PICS components of physical impairment, cognitive dysfunction, and mental illness. Results Among 414 eligible patients, 297 who received mechanical ventilation for 7 d or longer were examined. PICS was evaluated in 175 patients among them. High protein delivery on days 4–7 correlated with a low in-hospital mortality rate. In contrast, high protein delivery on days 1–3 correlated with physical impairment. A multivariate logistic regression analysis adjusted for age, sex, BMI, and severity revealed that average energy and protein deliveries on days 4–7 correlated with decreased in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99; P  = 0.013 and OR: 0.40; 95% CI: 0.17, 0.93; P  = 0.031, respectively). Nutrition delivery did not correlate with PICS outcomes after adjustments. In the multivariate regression using a restricted cubic spline model, in-hospital mortality monotonically decreased with increases in average nutrition delivery on days 4–7. Conclusions In patents with COVID-19 on mechanical ventilation for ≥7 d, nutrition delivery in the late period of the acute phase was monotonically associated with a decrease in in-hospital mortality. Adequate protein delivery is needed on days 4–7. This trial was registered at https://www.umin.ac.jp as UMIN000041276. [ABSTRACT FROM AUTHOR]

Background Polyphenols are antioxidants with promising anticancer properties, but few studies have examined the associations of specific dietary polyphenols with colorectal cancer (CRC) risks or among Black individuals in the United States. Objectives We examined the associations between dietary polyphenols and CRC and assessed differences in these associations or polyphenol intakes by subgroups, including race (Black and White), that may contribute to cancer disparities. Methods The Southern Community Cohort Study prospectively enrolled individuals from the southeastern United States during 2002–2009, most of whom had a low income or are Black. Validated FFQ data and polyphenol databases were used to estimate polyphenol intakes. Cox proportional hazards models were used to obtain HRs and 95% CIs for the highest compared to the lowest intake quintiles (Qs) of specific polyphenols. Median intakes of quintiles were used to obtain linear trends, and restricted cubic splines were used to obtain nonlinear trends. Subgroup analyses were conducted by cancer site, sex, race, household income, and BMI-defined obesity status. Results Among 71,599 participants, the median polyphenol intake was lower for Black individuals (452 mg/day; IQR, 277–672 mg/day) than White individuals (958 mg/day; IQR, 587–1597 mg/day). A significant, inverse, nonlinear association was observed for total polyphenol intake with the CRC risk (HR, 0.57; 95% CI, 0.38–0.86; P = 0.008 comparing 650 mg/day of intake to 0 mg/day). In addition, inverse linear associations were observed for tyrosols and the CRC risk (HRQ5vsQ1, 0.68; 95% CI, 0.50–0.91; P = 0.0014) and for hydroxybenzoic acids and the rectal cancer risk (HRQ5vsQ1, 0.49; 95% CI, 0.29–0.82; P = 0.0007). Associations were consistent by sex, race, income, and BMI. Conclusions Increasing intakes of total polyphenols, tyrosols, and hydroxybenzoic acids were associated with decreased CRC or rectal cancer risks, and associations were consistent across subgroups. Differences in polyphenol intakes may contribute to the increased CRC incidence among Black US individuals. [ABSTRACT FROM AUTHOR]

Background Conditioned food cues (e.g. smell, sight) can affect intake of foods associated with those cues, regardless of homeostatic need. As such, altering automatic associations with food cues could support weight loss or maintenance efforts by affecting the salience of those cues and the effort required to resist consumption. Objectives This study investigated neuronal and behavioral effects of an implicit priming (IP) intervention, in which negatively valenced images were paired with high-calorie foods and positively valenced images with low-calorie foods. Priming images were presented immediately before food images, but below conscious perception (20 ms). We hypothesized that this evaluative conditioning approach could alter food cue responses by modifying affective associations. Methods The final sample included 41 adults with BMI ≥25 kg/m2 (n  = 22, active IP; n  = 19, control IP). In control IP, food images were primed with neutral, scrambled images. Participants completed a visual food cue task during fMRI, both before and after IP. To determine the replicability of prior behavioral findings, food image ratings were completed before and after IP as a secondary outcome. Results In a whole-brain analysis, reduced dorsolateral prefrontal cortex (dlPFC) response to high-calorie foods was observed after active compared with control IP (t  = 4.93, P  = 0.033). With a region of interest analysis, reduced response to high-calorie foods in active compared with control IP was also observed in the striatum (t  = 2.40, P  = 0.009) and insula (t  = 2.38, P  = 0.010). Active compared with control IP was associated with reduced high-calorie food ratings (F  = 4.70, P  = 0.038). Conclusions Reduced insula and striatum response to high-calorie foods after active compared with control IP suggests effectiveness of IP in altering food cue salience. Reduced dlPFC response to high-calorie foods after active compared with control IP may reflect fewer attentional resources being directed to those images and reduced engagement of inhibitory processes. This trial was registered at clinicaltrials.gov as NCT02347527. [ABSTRACT FROM AUTHOR]

Background The serum natural abundance carbon isotope ratio (CIR) was recently identified as a candidate biomarker of animal protein intake in postmenopausal women. Such a biomarker would help clarify the relation between dietary protein source (plant or animal) and chronic disease risk. Objectives We aimed to evaluate the performance of the serum CIR as a biomarker of dietary protein source in a controlled feeding study of men and women of diverse age and BMI. Methods We conducted a 15-d feeding study of 100 adults (age: 18–70 y, 55% women) in Phoenix, AZ. Participants were provided individualized diets that approximated habitual food intakes. Serum was collected at the end of the feeding period for biomarker measurements. Results Median [IQR] animal protein intake was 67 g/d [55–88 g/d], which was 64% of total protein. The serum CIR was positively correlated with animal protein and inversely correlated with plant protein intake, leading to a strong correlation (r 2 = 0.76) with the dietary animal protein ratio (APR; animal/total protein). Regressing serum CIR on the APR, serum nitrogen isotope ratio (NIR), gender, age, and body weight generated an R 2 of 0.78. Following the measurement error model for predictive biomarkers, the resulting regression equation was then inverted to develop a calibrated biomarker equation for APR. Added sugars ratio (added/total sugars intake) and corn intakes also influenced the serum CIR but to a much lesser degree than the APR; variations in these intakes had only small effects on biomarker-estimated APR. Conclusions Based on our findings in this US cohort of mixed sex and age, we propose the serum CIR alongside NIR as a predictive dietary biomarker of the APR. We anticipate using this biomarker to generate calibrated estimates based on self-reported intake and ultimately to obtain more precise disease risk estimates according to dietary protein source. [ABSTRACT FROM AUTHOR]

Background Increasing evidence suggests that prevention of lifestyle diseases should begin early. Dairy protein and vitamin D can affect body composition and cardiometabolic markers, yet evidence among well-nourished children is sparse. Objectives We investigated combined and separate effects of high dairy protein intake and vitamin D on body composition and cardiometabolic markers in children. Methods In a 2 × 2–factorial, randomized trial, 200 white, Danish, 6–8-y-old children substituted 260 g/d dairy in their diet with high-protein (HP; 10 g protein/100 g) or normal-protein (NP; 3.5 g protein/100 g) yogurt and received blinded tablets with 20 µg/d vitamin D3 or placebo for 24 wk during winter. We measured body composition (by DXA), blood pressure, and fasting blood glucose, insulin, C-peptide, and lipids. Results In total, 184 children (92%) completed the study. Baseline median (25th–75th percentile) dairy protein intake was median: 3.7 (25th–75th percentile: 2.5–5.1) energy percentage (E%) and increased to median: 7.2 (25th–75th percentile: 4.7–8.8) E% and median: 4.2 (25th–75th percentile: 3.1–5.3) E% with HP and NP. Mean ± SD serum 25-hydroxyvitamin D concentration changed from 81 ± 17 to 89 ± 18 nmol/L and 48 ± 13 nmol/L with vitamin D and placebo, respectively. There were no combined effects of dairy protein and vitamin D, except for plasma glucose, with the largest increase in the NP–vitamin D group (P interaction = 0.005). There were smaller increases in fat mass index (P = 0.04) with HP than with NP, and the same pattern was seen for insulin, HOMA-IR, and C-peptide (all P = 0.06). LDL cholesterol was reduced with vitamin D compared with placebo (P < 0.05). Fat-free mass and blood pressure were unaffected. Conclusions High compared with normal dairy protein intake hampered an increase in fat mass index. Vitamin D supplementation counteracted the winter decline in 25-hydroxyvitamin D and the increase in LDL cholesterol observed with placebo. This study adds to the sparse evidence on dairy protein in well-nourished children and supports a vitamin D intake of ∼20 µg/d during winter. This trial was registered at clinicaltrials.gov as NCT03956732. [ABSTRACT FROM AUTHOR]

Background Understanding the relation between sustainability and nutrients is important in devising healthy and sustainable diets. However, there are no prevailing methodologies to assess sustainability at the nutrient level. Objectives The aim was to examine and demonstrate the potential of integrating input-output analysis with nutritional geometry to link environmental, economic, and health associations of dietary scenarios in Australia with macronutrients. Methods One-day dietary recalls of 9341 adult respondents (age ≥18 y) of the latest available cross-sectional National Nutrition and Physical Activity Survey–2011/12 of Australia were integrated with the input-output data obtained from the Australian Industrial Ecology Virtual Laboratory to calculate the environmental and economic impacts of dietary intakes in Australia. Australian adults' dietary intakes were classified into 3 dietary scenarios: "vegan," "pescatarian," and "omnivorous." Then, the relations between nutritional, economic, and environmental characteristics of the 3 dietary scenarios were demonstrated with the diets' macronutrient composition in a multidimensional nutritional geometry representation to link the sustainability indicators with macronutrients. Results Nutrient density and economic and environmental indicators increased as the percentage of energy from proteins increased and decreased as the percentage of energy from fats increased for the 3 dietary scenarios, except for the nutrient density and water use of the "vegan" dietary scenario. Energy density increased as the percentage of energy from fats increased and decreased as the percentage of energy from proteins increased for "pescatarian" and "omnivorous" dietary scenarios. In the "vegan" dietary scenario, nutrient density and water use increased as the percentage of energy from proteins increased; however, these decreased as the percentage of energy from carbohydrates increased, instead of fats. Conclusions The study presents a new approach to analyzing the relations between sustainability indicators, foods, and macronutrients and establishes that proteins, irrespective of the source of protein, are driving dietary environmental and economic impacts. [ABSTRACT FROM AUTHOR]

Background High–oleic acid (OA) vegetable oils are replacing some traditional vegetable oils in the US food supply. This may lead to reduced intake of the essential fatty acids (EFAs) linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3) in children, who need EFAs for growth and development and reduced risk for cardiometabolic disease into adulthood. Objectives The objectives of this study were the following: 1) to estimate trends in daily intake of EFAs among children aged 1–8 y, 2) identify top food sources of EFAs, and 3) evaluate the effects of replacing traditional oils with high-OA oils on meeting daily recommended intakes of EFAs. Methods Dietary data from 7814 children aged 1–8 y were acquired from the NHANES (2007–2016). Using a diet model, we evaluated the effect of replacing 20%, 40%, 60%, and 80% of traditional oils with high-OA oils on meeting adequate intakes (AIs) for EFAs. Results Major food sources of EFAs among all age–sex groups were grain dishes (35–40% of daily intake), meat and seafood dishes (17–21%), and fruit and vegetable dishes (12–14%). Replacing 40% or more of traditional oils with high-OA oil varieties will lead to inadequate daily intakes of EFAs. Conclusion Replacement of traditional vegetable oils with high-OA varieties will place children at risk of not meeting the AI levels for EFAs. A balanced approach of including traditional oils and high-OA oils in the US food supply is needed to prevent inadequate intakes of EFAs in children. [ABSTRACT FROM AUTHOR]

Background Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity have been limited and inconsistent. Objective We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infection and COVID-19 severity. Methods We used data from periodic surveys (May 2020 to March 2021) within the Nurses' Health Study II. Among 39,315 participants, 1768 reported a positive test for SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a semiquantitative, pre-pandemic food-frequency questionnaire in 2015. Predicted 25-hydroxyvitamin D [25(OH)D] concentration were calculated based on a previously validated model including dietary and supplementary vitamin D intake, UV-B, and other behavioral predictors of vitamin D status. Results Higher predicted 25(OH)D concentrations, but not vitamin D intake, were associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest quintile of predicted 25(OH)D concentrations with the lowest, the multivariable-adjusted OR was 0.76 (95% CI: 0.58, 0.99; P -trend = 0.04). Participants in the highest quartile of UV-B (OR: 0.76; 95% CI: 0.66, 0.87; P -trend = 0.002) and UV-A (OR: 0.76; 95% CI: 0.66, 0.88; P -trend < 0.001) also had a lower risk of SARS-CoV-2 infection compared with the lowest. High intake of vitamin D from supplements (≥400 IU/d) was associated with a lower risk of hospitalization (OR: 0.51; 95% CI: 0.29, 0.91; P -trend = 0.04). Conclusions Our study provides suggestive evidence on the association between higher predicted circulating 25(OH)D concentrations and a lower risk of SARS-CoV-2 infection. Greater intake of vitamin D supplements was associated with a lower risk of hospitalization. Our data also support an association between exposure to UV-B or UV-A, independently of vitamin D and SARS-CoV-2 infection, so results for predicted 25(OH)D need to be interpreted cautiously. [ABSTRACT FROM AUTHOR]

Background Longer-term consumption of SFA-reduced, MUFA-enriched dairy products has been reported to improve fasting flow-mediated dilatation (FMD). Yet, their impact on endothelial function in the postprandial state warrants investigation. Objectives The aim was to compare the impact of a fatty acid (FA) modified with a conventional (control) dairy diet on the postprandial %FMD (primary outcome) and systemic cardiometabolic responses to representative meals, and retrospectively explore whether treatment effects differ by apolipoprotein E (APOE) or endothelial NO synthase (eNOS) Glu298Asp gene polymorphisms. Methods In a crossover-design randomized controlled study, 52 adults with moderate cardiovascular disease risk consumed dairy products [38% of total energy intake (%TE) from fat: FA-modified (target: 16%TE SFAs; 14%TE MUFAs) or control (19%TE SFAs; 11%TE MUFAs)] for 12 wk, separated by an 8-wk washout. Blood sampling and FMD measurements (0–480 min) were performed pre- and postintervention after sequential mixed meals that were representative of the assigned dairy diets (0 min, ∼50 g fat; 330 min, ∼30 g fat). Results Relative to preintervention (∆), the FA-modified dairy diet and meals (treatment) attenuated the increase in the incremental AUC (iAUC), but not AUC, for the %FMD response observed with the conventional treatment (–135 ± 69% vs. +199 ± 82% × min; P = 0.005). The ∆ iAUC, but not AUC, for the apoB response decreased after the FA-modified treatment yet increased after the conventional treatment (–4 ± 3 vs. +3 ± 3 mg/mL × min; P = 0.004). The ∆ iAUC decreased for plasma total SFAs (P = 0.003) and trans 18:1 (P < 0.0001) and increased for cis -MUFAs (P < 0.0001) following the conventional relative to the FA-modified treatment. No treatment × APOE or eNOS genotype interactions were evident for any outcome. Conclusions This study provides novel insights into the longer-term effects of FA-modified dairy food consumption on postprandial cardiometabolic responses. [ABSTRACT FROM AUTHOR]

Background PUFAs may influence the risk of asthma; however, long-term prospective studies including objective biomarkers of PUFA intake are lacking. Objectives The objective was to investigate the role of dietary intake and plasma concentrations of n–3 and n–6 (ω-3 and ω-6) PUFAs in childhood and adolescence for the development of asthma and lung function up to young adulthood. Methods The study included participants from the Swedish prospective birth cohort BAMSE. Dietary intake of PUFAs was calculated from FFQs (n  = 1992) and plasma proportions of PUFAs were measured in phospholipids (n  = 831). We analyzed the n–3 PUFA α-linolenic acid (ALA; 18:3n–3); the sum of very-long-chain (VLC) n–3 PUFAs: EPA (20:5n–3), DHA (22:6n–3), and docosapentaenoic acid (22:5n–3); and the n–6 PUFAs linoleic acid (LA; 18:2n–6) and arachidonic acid (AA; 20:4n–6). Asthma was assessed by questionnaires at 8, 16, and 24 y and lung function was measured by spirometry at 24 y. Results A high (≥median) self-reported dietary intake of LA at 8 y and AA at 16 y was associated with increased risk of prevalent asthma at 24 y (OR: 1.41; 95% CI: 1.10, 1.82 and OR: 1.32; 95% CI: 1.02, 1.70, respectively). In contrast, plasma proportions of ALA, ∑VLC n–3 PUFAs, and AA at 8 y, as well as LA at 16 y, were inversely associated with prevalent asthma at 24 y (e.g. OR: 0.55; 95% CI: 0.38, 0.81 for ∑VLC n–3 PUFAs). No consistent associations were observed with lung function. Conclusions High dietary intake of certain n–6 PUFAs in childhood or adolescence may be associated with increased risk of asthma up to young adulthood, whereas dietary biomarkers of certain n–3 and n–6 PUFAs in plasma may be associated with decreased risk. Thus, the role of diet compared with altered metabolism of PUFAs needs further investigation to improve dietary preventive strategies for asthma. [ABSTRACT FROM AUTHOR]

Background The 2019 Canada's Food Guide (CFG) recommends that foods containing mostly unsaturated fatty acid (UFA) should replace foods that contain mostly SFA to reduce SFA intakes. Objectives The objective of this study was to model the theoretical changes in intake of SFA at the population level if all Canadians adhered to that recommendation. Methods Dietary intakes from 24-h recalls in the nationally representative 2015 Canadian Community Health Survey–Nutrition were used for these analyses. Foods identified as high in SFA based on Health Canada's criteria [≥2 g SFA per reference amount and/or ≥15% of energy (%E) of the food's content as SFA] were replaced by an equal amount (gram per gram) of substitution foods that were lower in SFA and had a higher UFA to SFA ratio. Distributions of SFA and other nutrients before and after substitutions were estimated using the National Cancer Institute (NCI) method based on dietary intakes data from a 24-h recall repeated in 37% of the population. Results The mean (95% CI) dietary SFA intake among Canadians 2 y or older would be theoretically reduced from 10.8%E (10.7, 11.0%E) to 5.8%E (5.7, 5.9%E) if all high-SFA foods consumed were replaced by the corresponding low-SFA/high-UFA foods. Modeled usual intake of SFA after substitution was <10%E in 100% of Canadians, irrespective of sex and age. Almost half (44%) of the modeled reduction in SFA intake was attributed to replacement of SFA-rich foods not recommended in the 2019 CFG. Conclusions This food-based substitution modeling analysis suggests that consumption of SFA would be below 10%E in Canada if all Canadians adhered to the 2019 CFG recommendation that foods containing mostly UFA should replace foods that contain mostly SFA. [ABSTRACT FROM AUTHOR]

Background Gastrointestinal enteroendocrine cells express chemosensory bitter taste receptors that may play an important role in regulating energy intake (EI) and gut function. Objectives To determine the effect of a bitter hop extract (Humulus lupulus L.) on acute EI, appetite, and hormonal responses. Methods Nineteen healthy-weight men completed a randomized 3-treatment, double-blind, crossover study with a 1-wk washout between treatments. Treatments comprised either placebo or 500 mg of hop extract administered in delayed-release capsules (duodenal) at 11:00 h or quick-release capsules (gastric) at 11:30 h. Ad libitum EI was recorded at the lunch (12:00 h) and afternoon snack (14:00 h), with blood samples taken and subjective ratings of appetite, gastrointestinal (GI) discomfort, vitality, meal palatability, and mood assessed throughout the day. Results Total ad libitum EI was reduced following both the gastric (4473 kJ; 95% CI: 3811, 5134; P = 0.006) and duodenal (4439 kJ; 95% CI: 3777, 5102; P = 0.004) hop treatments compared with the placebo (5383 kJ; 95% CI: 4722, 6045). Gastric and duodenal treatments stimulated prelunch ghrelin secretion and postprandial cholecystokinin, glucagon-like peptide 1, and peptide YY responses compared with placebo. In contrast, postprandial insulin, glucose-dependent insulinotropic peptide, and pancreatic polypeptide responses were reduced in gastric and duodenal treatments without affecting glycemia. In addition, gastric and duodenal treatments produced small but significant increases in subjective measures of GI discomfort (e.g. nausea, bloating, abdominal discomfort) with mild to severe adverse GI symptoms reported in the gastric treatment only. However, no significant treatment effects were observed for any subjective measures of appetite or meal palatability. Conclusions Both gastric and duodenal delivery of a hop extract modulates the release of hormones involved in appetite and glycemic regulation, providing a potential "bitter brake" on EI in healthy-weight men. [ABSTRACT FROM AUTHOR]

Background The association between total protein intake and all-cause mortality is inconsistent. Pneumonia is a major cause of death among the elderly, and the association between protein intake and pneumonia mortality warrants clarification. Objectives We aimed to examine the association between total, plant, and animal protein intake and pneumonia mortality in a prospective design. Methods The Japan Public Health Center (JPHC)–based Prospective Study prospectively follows 83,351 participants (37,652 men and 45,699 women). Total, plant, and animal protein intakes were calculated from a validated food-frequency questionnaire. A Cox hazards model was used to calculate HRs and 95% CIs, with adjustment for confounding factors. Results During ∼18.4 y of follow-up, 990 pneumonia deaths (634 men and 356 women) were observed. In the multivariable-adjusted model and in the model further adjusted for fatty acid intake, increase in total protein intake was marginally significantly associated with lower pneumonia mortality in women [lowest vs. highest quartile, HR (95% CI): 0.71 (0.53, 0.97), P -trend = 0.01 in the multivariable-adjusted model, and 0.70 (0.45, 1.06), P -trend = 0.05 in the fatty acid intake–adjusted model]. Total protein intake in men and animal and plant protein intake in both men and women were not significantly associated with pneumonia mortality in the fatty acid–adjusted model. Conclusions Although the HR in the highest quartile was not significant and further research to determine the upper limit of recommended protein intake is required, higher total protein intake was associated with lower pneumonia mortality in women. [ABSTRACT FROM AUTHOR]

Background Prepregnancy overweight and excessive gestational weight gain (GWG) increase the risk of complications and offspring obesity. Objectives We aimed to investigate the effect of a high-protein low–glycemic index (HPLGI) diet on GWG, birth weight, and risk of gestational complications in pregnant women with obesity. Methods A total of 279 women with prepregnancy overweight or obesity (BMI: 28–45 kg/m2), between 18 and 45 y old, and in their late first trimester with singleton pregnancies, were randomly assigned to 1 of 2 ad libitum diets: a high-protein low–glycemic index diet (HPLGI: 25%–28% of energy from protein and glycemic index ≤ 55) and a moderate-protein moderate–glycemic index diet (MPMGI: 15%–18% of energy from protein and glycemic index ∼60). Diets were consumed from gestational week 15 and throughout pregnancy. Participants received dietary guidance by a clinical dietician 9 times to facilitate adherence. Results Out of 141 and 138 women randomly assigned to the HPLGI and MPMGI diets, 105 and 104 completed the intervention, respectively (75%). In the available case analyses, GWG was 6.8 ± 1.3 kg among women assigned the HPLGI diet and this was significantly lower, by −1.7 kg (95% CI: −2.8, −0.5 kg; P = 0.004), than the GWG of 8.5 ± 1.3 kg among women assigned the MPMGI diet. There were no significant differences between diets on major neonatal outcomes (birth weight and other anthropometric measures). The incidence of composite pregnancy complications was lower for the HPLGI than for the MPMGI diet (35.4% compared with 53.7%, respectively; P = 0.009), including cesarean delivery (15.4% compared with 28.8%, respectively; P = 0.03). There were no reported maternal, fetal, or neonatal deaths. Incidence of miscarriages (1%–2%) did not differ between groups. Conclusions A moderate increase in dietary protein in conjunction with a reduction in glycemic index during the last 2 trimesters of pregnancy reduced GWG and limited complications and cesarean deliveries among women with overweight or obesity. [ABSTRACT FROM AUTHOR]

Background Cardiovascular diseases (CVDs) are a major cause of deaths worldwide, but prospective data on dietary risk factors for CVD in South and Southeast Asian populations are sparse. Objective We aimed to evaluate the relation between macronutrient and food intakes and incidence of major adverse cardiovascular events (MACEs) in a multi-ethnic Asian population. Methods We used data from the Singapore Multi-Ethnic Cohort (n  = 12,408), a prospective cohort of ethnic Chinese, Malay, and Indian adults aged 21‒65 y recruited between 2004 and 2010. Dietary intakes were assessed using a validated food-frequency questionnaire, and the incidence of MACEs was ascertained through data linkage with national registries. A Cox proportional hazards model was used to evaluate the associations between dietary intakes and MACE risk. Results Over a mean (SD) follow-up of 10.1 (2.3) y, 746 incident cases of MACEs were documented. We observed a direct association between carbohydrate intake and MACE risk (highest vs. lowest quartile, HR: 1.35; 95% CI: 1.07, 1.71; P -trend = 0.001). Replacing 5% of energy from carbohydrate with polyunsaturated fat (HR: 0.79; 95% CI: 0.69, 0.91) but not saturated fat (HR: 0.95; 95% CI: 0.84, 1.09) was significantly associated with a lower MACE risk. In terms of food groups, replacing 1 serving/d of refined grains with fruit (HR: 0.93; 95% CI: 0.87, 0.99), vegetables (HR: 0.92; 95% CI: 0.85, 1.00), and dairy (HR: 0.90; 95% CI: 0.82, 0.98) was associated with lower MACE risk. Cholesterol intake was associated with a higher MACE risk in ethnic Indians (highest vs. lowest quartile, HR: 2.40; 95% CI: 1.53, 3.75; P -trend < 0.001) but not in ethnic Malay or Chinese (P -interaction = 0.015). Conclusions Moderating carbohydrate intakes by increasing polyunsaturated fat intake and replacing refined grains with fruits, vegetables, and dairy was associated with lower MACE risk in Asian populations. [ABSTRACT FROM AUTHOR]

Background There remains a limited understanding of the metabolic perturbations, beyond phenylalanine (Phe) metabolism, that contribute to phenotypic variability in phenylketonuria (PKU). Objectives This study aimed to characterize changes in the PKU plasma metabolome following a 5-d metabolic camp intervention and to compare PKU profiles with those of matched healthy controls. Methods In 28 females (aged 12–57 y), fasting plasma samples were collected on the first (day 1) and final (day 5) days of camp to measure metabolic control and to complete untargeted metabolomic profiling. Three-day dietary records were collected to assess changes in dietary adherence and composition. Univariate (Wilcoxon signed-rank and Mann–Whitney U test) and multivariate (random forest, hierarchical clustering) analyses were performed to identify clinical and metabolic features that were associated with the intervention and disease state. Results Relative to healthy controls, Phe catabolites, ketones, and carnitine- and glycine-conjugated fatty acids were elevated in females with PKU at baseline, whereas fatty acylcholine metabolites were substantially lower. After the camp intervention, plasma Phe concentrations decreased [median change: –173 µmol/L (IQR: –325, –28 µmol/L)] and 70% of PKU participants demonstrated improved dietary adherence by decreasing Phe intake and/or increasing medical food consumption. This was accompanied by a shift in abundance for 223 metabolites (q  < 0.05). Compounds associated with the metabolism of Phe, fatty acids, and choline contributed most to profile differences between camp days 1 and 5. Conclusions In females with PKU, untargeted metabolomics identified prominent perturbations in amino acid and lipid metabolites associated with bioenergetic impairment and oxidative stress. Choline-conjugated lipids could have fundamental roles in these pathways and they have not been previously evaluated in PKU. A short-term camp intervention was effective for improving or fully normalizing the abundance of the identified discriminatory metabolites. [ABSTRACT FROM AUTHOR]

Background Current global food systems threaten human health and environmental sustainability. In 2019, the EAT-Lancet Commission on healthy diets from sustainable food systems defined the first global reference diet to improve both areas, but there is no consensus on how to quantify the EAT-Lancet reference diet as a diet index, and its relation to mortality has not been widely studied. Objectives We sought to develop a new dietary index to quantify adherence to the EAT-Lancet diet and assess its association with mortality in a large, population-based Swedish cohort. We also examined food components included in the index and their individual associations with mortality. Methods We used the Malmö Diet and Cancer cohort (n  = 22,421; 45–73 years old at baseline). Dietary data were collected using a modified diet history method. The EAT-Lancet index was developed based on intake levels and reference intervals of 14 food components defined in the EAT-Lancet diet (0–3 points per component; 0–42 points in total). Associations with mortality were examined based on registers during a mean of 20 years of follow-up and were adjusted for potential confounders. Results Divided into 5 adherence groups, the highest adherence to the EAT-Lancet diet (≥23 points) was associated with lower all-cause mortality (HR, 0.75; 95% CI, 0.67–0.85), cancer mortality (HR, 0.76; 95% CI, 0.63–0.92), and cardiovascular mortality (HR, 0.68; 95% CI, 0.54–0.84) than the lowest adherence (≤13 points). Several food components included in the index contributed to the observed reductions in mortality. Conclusions We developed a new dietary index to investigate adherence to the EAT-Lancet diet. The findings indicate a 25% lower risk of mortality among those with the highest adherence to the EAT-Lancet diet, as defined using our index, which adds to the evidence base for the development of sustainable dietary guidelines. [ABSTRACT FROM AUTHOR]

Background The association of meat consumption with gastric cancer is inconclusive. Objectives We examined the association of meat consumption with gastric cancer risk among Japanese men and women. Methods This cohort study included 42,328 male and 48,176 female participants of the Japan Public Health Center–based Prospective Study, who were aged 45 to 74 y at recruitment. Dietary intake data were collected from 1 January 1995 to 31 December 1999 using a validated food-frequency questionnaire. HRs and 95% CIs for gastric cancer were estimated using Cox proportional hazards regression models. Results During a mean follow-up of 15 y, 1868 male and 833 female incident gastric cancer cases were identified. Intake of total and subtypes of meat was not associated with total gastric cancer. However, higher chicken consumption was associated with reduced distal gastric cancer risk in women (HR for quintile 5 vs. quintile 1: 0.75; 95% CI: 0.56, 0.99; P- trend = 0.027), with a similar but nonsignificant risk reduction among women with Helicobacter pylori (HR: 0.59; 95% CI: 0.29, 1.20; P- trend = 0.06) in subgroup analysis. Conclusions Meat consumption was not associated with total gastric cancer risk. [ABSTRACT FROM AUTHOR]

Background Population-based studies generally show J-shaped associations between alcohol intake and mortality from cardiovascular disease (CVD). Little is known about alcohol and long-term mortality risk after myocardial infarction (MI). Objectives We examined alcohol intake in relation to all-cause, CVD, and ischemic heart disease (IHD) mortality in Dutch post-MI patients of the Alpha Omega Cohort. Methods The analysis comprised 4365 patients (60–80 years; 79% male) with an MI  ≤ 10 years before study enrolment. We used a 203-item FFQ to assess alcohol (total ethanol) and dietary intakes over the past month. Patients were classified as nondrinkers (0 g/d; n  = 956) or very light (>0 to 2 g/d; n  = 385), light (M: >2 to 10 g/d; F: >2 to 5 g/d; n  = 1125), moderate (M: >10 to 30 g/d; F: >5 to 15 g/d; n  = 1207), or heavy drinkers (M: >30 g/d; F: >15 g/d; n  = 692). HRs of mortality for alcohol intake were obtained from Cox models, adjusting for age, sex, education, smoking, BMI, physical activity, and dietary factors. Results Alcohol was consumed by 83% of males and 61% of females. During ∼12 years of follow-up, 2035 deaths occurred, of which 903 were from CVD and 558 were from IHD. Compared to the (combined) reference group of nondrinkers and very light drinkers, HRs for all-cause mortality were 0.87 (95% CI, 0.78–0.98), 0.85 (95% CI, 0.75–0.96), and 0.91 (95% CI, 0.79–1.04) for light, moderate, and heavy drinkers, respectively. For CVD mortality, corresponding HRs were 0.80 (95% CI, 0.67–0.96), 0.82 (95% CI, 0.69–0.98), and 0.87 (95% CI, 0.70–1.08) for light, moderate, and heavy drinkers, respectively. Findings for IHD mortality were similar. HRs did not materially change when nondrinkers or very light drinkers were taken as the reference, or after exclusion of former drinkers or patients with diabetes or poor/moderate self-rated health. Conclusions Light and moderate alcohol intakes were inversely associated with mortality risk in stable post-MI patients. These observational findings should be cautiously interpreted in light of the total evidence on alcohol and health. The Alpha Omega Cohort is registered at clinicaltrials.gov as NCT03192410. [ABSTRACT FROM AUTHOR]

Background The increasing colorectal cancer (CRC) survivor population highlights the need for dietary recommendations in order to enhance health-related quality of life (HRQoL) and alleviate symptoms of fatigue, chemotherapy-induced peripheral neuropathy (CIPN), and gastrointestinal problems. Objectives Because of the therapeutic potential of dietary fiber on the gut, we aim to assess longitudinal associations of postdiagnostic dietary fiber, fruit, and vegetable intake, a major source of dietary fiber, with HRQoL, fatigue, CIPN, and gastrointestinal symptoms in CRC survivors from 6 wk to 24 mo posttreatment. Methods In a prospective cohort among stage I–III CRC survivors (n = 459), 5 repeated study measurements between diagnosis and 24 mo posttreatment were executed. Dietary fiber intake and fruit and vegetable intake were measured by 7-d dietary records. HRQoL, fatigue, CIPN, and gastrointestinal symptoms were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyze longitudinal associations from 6 wk until 24 mo posttreatment and used hybrid models to disentangle the overall association into intraindividual changes and interindividual differences over time. Results Higher dietary fiber intake and fruit and vegetable intake were longitudinally associated with statistically significant better physical functioning and less fatigue. Intraindividual analyses showed that an increase of 10 g/d in dietary fiber within individuals over time was associated with better physical functioning (β: 2.3; 95% CI: 0.1, 4.4), role functioning (ability to perform daily activities; 5.9; 1.5, 10.3), and less fatigue (−4.1; −7.7, −0.5). An average increase in fruit and vegetable intake of 100 g/d between individuals over time was predominantly associated with less fatigue (−2.2; −4.2, −0.3). No associations were found with CIPN and gastrointestinal symptoms. Conclusions Our results suggest that increasing dietary fiber, fruit, and vegetable intake is related to better physical and role functioning and less fatigue in the first 2 y after the end of treatment for CRC. [ABSTRACT FROM AUTHOR]

Background Since several lines of evidence suggest that estrogens may be involved in lung carcinogenesis, it has been hypothesized that intake of phytoestrogens, similar in molecular structure to mammalian estrogens, may be associated with lung cancer development. Objective The aim was to prospectively evaluate the association between phytoestrogen exposure and lung cancer risk in never-smoking women. Methods We conducted a nested case-control study within a population-based prospective cohort study of women. A total of 478 incident lung cancer cases and their individually matched controls were identified among never-smoking women after a mean follow-up of 15.6 years. Habitual intake of and internal exposure to phytoestrogens were assessed by repeated dietary surveys and urinary biomarkers, respectively. ORs and 95% CIs for lung cancer were estimated in conditional logistic regression models. Results After adjustment for potential confounders, a moderate intake of dietary isoflavones was inversely associated with lung cancer risk in never-smoking women, with the OR for the second quartile vs. the lowest quartile of intake being 0.52 (95% CI: 0.35, 0.76). Further increasing intake did not convey additional benefits, with ORs (95% CI) for the third and fourth quartiles of 0.53 (0.36, 0.78) and 0.47 (0.31, 0.72), respectively (P -overall < 0.001 and P -nonlinearity = 0.006). A similar association was seen when exposure to isoflavones was assessed by urinary biomarkers. ORs (95% CI) for the second, third, and fourth quartiles compared with the lowest quartile of urinary isoflavone excretion were 0.57 (0.39, 0.83), 0.64 (0.44, 0.92), and 0.60 (0.41, 0.86), respectively. The inverse association reached a plateau beyond the second quartile, with P -overall = 0.04 and P -nonlinearity = 0.15. Urinary excretion of gut-microbiota–derived metabolites of lignans was not related to lung cancer risk. Conclusions This study suggests that moderately increasing intake of isoflavone-rich foods is associated with lower risk of lung cancer in never-smoking women. [ABSTRACT FROM AUTHOR]

Background Increased protein intake is suggested as a strategy to slow or reverse the loss of muscle mass and strength observed in sarcopenia, but results from studies that directly tested this possibility have been inconsistent. Objectives We assessed the evidence on the effects of whole protein supplementation or higher-protein diets, without the use of amino acids or supplements known to stimulate hypertrophy, alone or in combination with resistance exercise (RE) interventions, on lean body mass (LBM) and strength in older adults. Methods A systematic search was conducted using PubMed, Medline, Web of Science, and Cochrane CENTRAL databases from January 1990 to July 2021. Randomized controlled trials that assessed the effects of protein supplementation and/or higher-protein dietary interventions in older adults (mean age ≥50 y) on total LBM, appendicular lean mass (ALM), and handgrip (HG) and knee extension (KE) strength were included. Results Twenty-eight studies were identified. In pooled analysis, compared with lower protein controls, protein supplementation did not have a significant positive effect on total LBM [weighted mean difference in change (WMD): 0.34; 95% CI: –0.21, 0.89; I 2 = 90.01%], ALM (WMD: 0.4; 95% CI: –0.01, 0.81; I 2 = 90.38%), HG strength (WMD: 0.69; 95% CI: –0.69, 2.06; I 2 = 94.52%), or KE strength (WMD: 1.88; 95% CI: –0.6, 4.35; I 2 = 95.35%). However, in interventions that used also RE, statistically significant positive effects of protein were observed for ALM (WMD: 0.54; 95% CI: 0.03, 1.05; I 2 = 89.76%) and HG (WMD: 1.71; 95% CI: 0.12, 3.30; I 2 = 88.71%). Meta-regression revealed no significant association between age, per-meal protein dose, duration, and baseline protein intake with change in any outcome. Subgroup analysis revealed the statistically significant effects on ALM occurred only in sarcopenic/frail populations (WMD: 0.88; 95% CI: 0.51, 1.25; I 2 = 79.0%). Most studies (n  = 22) had some risk of bias. Conclusions In older adults performing RE, increased protein intake leads to greater ALM and HG strength compared with lower protein controls. Without RE, protein has no additional benefit on changes in total LBM, ALM, or HG strength. [ABSTRACT FROM AUTHOR]

Background Circulating 25-hydroxyvitamin D [25(OH)D] has been the accepted vitamin D exposure/intake biomarker of choice within recent DRI exercises, but use of other vitamin D–related biomarkers as well as functional markers has been suggested. These may be of value in future vitamin D DRI exercises, such as the FAO/WHO's one for young children. Objectives To systematically review the usefulness of circulating 25(OH)D, parathyroid hormone (PTH), free and bioavailable 25(OH)D, C3-epimer of 25(OH)D, vitamin D3, 24,25-dihydroxyvitamin D [24,25(OH)2D], and bone turnover markers and calcium absorption as vitamin D biomarkers for DRI development in children. Methods Methods included structured searches of published articles, full-text reviews, data extraction, quality assessment, meta-analysis, and random-effects meta-regression. Results Fifty-nine vitamin D supplementation randomized controlled trials (RCTs) were included (39 in infants/children as the priority group and the remainder in adults since pediatric studies were absent/limited). Vitamin D supplementation significantly raised circulating 25(OH)D in infants and children, but the response was highly heterogeneous [weighted mean difference (WMD): 27.7 nmol/L; 95% CI: 22.9, 32.5; 27 RCTs; I 2 = 93%]. Meta-regression suggested an increase by 1.7 nmol/L (95% CI: 0.7, 2.6) in serum 25(OH)D per each 100-IU increment in vitamin D intake (P  = 0.0005). Vitamin D supplementation had a significant effect on circulating 24,25(OH)2D (WMD: 3.4 nmol/L; 95% CI: 2.4, 4.5; 13 RCTs; I 2 = 95%), with a dose–response relation (+0.15 nmol/L per 100 IU; 95% CI: –0.01, 0.29). With circulating PTH, although there was a significant effect of vitamin D on WMD (P  = 0.05), there was no significant dose–response relation (P  = 0.32). Pediatric data were too limited in relation to the usefulness of the other biomarkers. Conclusions Circulating 25(OH)D may be a useful biomarker of vitamin D exposure/intake for DRI development in infants and children. Circulating 24,25(OH)2D also showed some promise, but further data are needed, especially in infants and children. [ABSTRACT FROM AUTHOR]

Background Recent observational studies have suggested that circulating phosphorus concentrations are positively associated with the risk of prostate cancer. However, little is known about the causal direction of the association. Objectives To explore the potential causal relation between circulating phosphorus and risk of prostate cancer, we conducted a Mendelian randomization (MR) study. Methods Summary statistics of prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWASs) consisting of 79,148 cases and 61,106 controls. Single-nucleotide polymorphisms (SNPs) associated with serum phosphorus concentration were selected from a GWAS of 291,408 individuals from the UK Biobank. MR analysis was performed using the inverse variance weighted (IVW) method, supplemented with simple median method, weighted median method, maximum likelihood–based method, MR-Egger regression, and the MR pleiotropy residual sum and outlier test. We also performed a meta-analysis of observational studies to assess the associations of dietary phosphorus intake and serum phosphorus concentration with risk of prostate cancer. Results In the MR analysis, a total of 125 independent SNPs associated with serum phosphorus concentrations were used as instrumental variables. Genetically predicted serum phosphorus concentrations were associated with a 19% increased risk of prostate cancer (95% CI: 9%, 31%) per 1-SD increment of serum phosphorus by IVW (P  = 1.82 × 10–4). Sensitivity analyses using alternative MR methods produced similar positive associations, and no evidence of pleiotropy was detected by MR-Egger regression (P  = 0.422). For meta-analysis, 8 studies for dietary phosphorus intake and 4 for serum phosphorus concentrations were included involving a total of 669,080 participants. Consistently, high dietary phosphorus intake and serum phosphorus concentrations were associated with an 8% (95% CI: 4%, 12%) and 7% (95% CI: 1%, 14%) increase in prostate cancer risk, respectively. Conclusions Our study suggested a potential causal relation between circulating phosphorus and risk of prostate cancer. Further studies are warranted to elucidate the underlying mechanism of phosphorus in the development of prostate cancer. [ABSTRACT FROM AUTHOR]

Background Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on the elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed. Objectives The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS-severity scoring system (IBS-SSS). Methods The study was carried out with a double-blind, placebo-controlled, randomized 3-way crossover design in a clinical facility in Uppsala from September 2018 to June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomly assigned; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomly assigned to 1-wk interventions with FODMAPs (50 g/d), gluten (17.3 g/d), or placebo, separated by 1-wk washout. All participants who completed ≥1 intervention were included in the intention-to-treat analysis. Results In participants with IBS (n  = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI: 222, 257]) than placebo (198 [180, 215]; P  = 0.00056) or gluten (208 [190, 226]; P  = 0.013); no differences were found between the placebo and gluten groups (P  = 1.0). There were large interindividual differences in IBS-SSS scores associated with treatment. No adverse events were reported. Conclusion In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large interindividual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. This trial was registered at www.clinicaltrials.gov as NCT03653689. [ABSTRACT FROM AUTHOR]

Background Iodine intake in populations is usually assessed by measuring urinary iodine concentrations (UICs) in spot samples. Hot climate conditions may reduce urine volume, thus leading to overestimations of UIC and thereby masking inadequate iodine intake. Objectives We investigated the effects of season on UICs in 2 populations exposed to high-temperature climates. Methods In this observational study, we examined women (18–49 years) in Tanzania (n cold = 206; n hot = 179) and South Africa (n cold = 157; n hot = 126) during cold and hot seasons. From each woman in both seasons, we obtained two 24-hour urine collections and 2 spot urine samples, as well as salt, water, and cow's milk samples. We measured the urine volume, UIC, and urinary creatinine concentration (UCC). The 24-hour urinary iodine excretion (UIE) was calculated and used to estimate the iodine intake. We used linear mixed-effects models to test for differences between seasons. Results In Tanzanian women, we observed no seasonal effect on the urine volume, 24-hour UIE, 24-hour UIC, spot UIC, spot UIC:UCC ratio, or salt iodine concentration. In South African women, the median 24-hour urine volume was 1.40 L (IQR, 0.96–2.05 L) in the winter and 15% lower in the summer (P  < 0.001). The median 24-hour UIE was 184 µg/day (IQR, 109–267 µg/day) in the winter and 34% lower in the summer (P  < 0.001), indicating a lower iodine intake. As a result, UICs did not significantly differ between seasons in 24-hour collections and spot samples, whereas the spot UIC:UCC ratio differed by 21% (P  < 0.001) and reflected the lower iodine intake. In both study populations, the within- and between-person variabilities in urine volume, 24-hour UICs, and spot UICs were higher than the variability between seasons. Conclusions Spot UIC may slightly overestimate the iodine intake in hot temperatures due to concentrated urine, and methods to correct for urine volume may be considered. Local seasonal differences in iodine intakes may also occur in some populations. This trial was registered at http://www.clinicaltrials.gov as NCT03215680. [ABSTRACT FROM AUTHOR]

Background Dicarbonyls are highly reactive compounds and major precursors of advanced glycation end products (AGEs). Both dicarbonyls and AGEs are associated with development of age-related diseases. Dicarbonyls are formed endogenously but also during food processing. To what extent dicarbonyls from the diet contribute to circulating dicarbonyls and AGEs in tissues is unknown. Objectives To examine cross-sectional associations of dietary dicarbonyl intake with plasma dicarbonyl concentrations and skin AGEs. Methods In 2566 individuals of the population-based Maastricht Study (age: 60 ± 8 y, 50% males, 26% with type 2 diabetes), we estimated habitual intake of the dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) by combining FFQs with our dietary dicarbonyl database of MGO, GO, and 3-DG concentrations in > 200 commonly consumed food products. Fasting plasma concentrations of MGO, GO, and 3-DG were measured by ultra-performance liquid chromatography–tandem mass spectrometry. Skin AGEs were measured as skin autofluorescence (SAF), using the AGE Reader. Associations of dietary dicarbonyl intake with their respective plasma concentrations and SAF (all standardized) were examined using linear regression models, adjusted for age, sex, potential confounders related to cardiometabolic risk factors, and lifestyle. Results Median intake of MGO, GO, and 3-DG was 3.6, 3.5, and 17 mg/d, respectively. Coffee was the main dietary source of MGO, whereas this was bread for GO and 3-DG. In the fully adjusted models, dietary MGO was associated with plasma MGO (β: 0.08; 95% CI: 0.02, 0.13) and SAF (β: 0.12; 95% CI: 0.07, 0.17). Dietary GO was associated with plasma GO (β: 0.10; 95% CI: 0.04, 0.16) but not with SAF. 3-DG was not significantly associated with either plasma 3-DG or SAF. Conclusions Higher habitual intake of dietary MGO and GO, but not 3-DG, was associated with higher corresponding plasma concentrations. Higher intake of MGO was also associated with higher SAF. These results suggest dietary absorption of MGO and GO. Biological implications of dietary absorption of MGO and GO need to be determined. The study has been approved by the institutional medical ethical committee (NL31329.068.10) and the Minister of Health, Welfare and Sports of the Netherlands (Permit 131088–105234-PG). [ABSTRACT FROM AUTHOR]

Background A large proportion of infants in low- and middle-income countries are stunted. These infants are often fed complementary foods that are low-quality, primarily in terms of protein and micronutrients. Objectives We aimed to test 2 milk–cereal mixes supplemented with modest and high amounts of protein during 6–12 mo of age, compared with no supplementation, for their effect on length-for-age z score (LAZ) at 12 mo of age. Methods Eligible infants (6 mo plus ≤29 d) were randomly assigned to either of the 2 interventions (modest- and high-protein) or a no supplement group. The milk–cereal mixes provided ∼125 kcal, 30%–45% energy from fats, and 80%–100% RDA of multiple micronutrients (MMN). The modest-protein group received 2.5 g protein [protein energy ratio (PER): 8%; 0.75 g from milk source] and the high-protein group received 5.6 g protein (PER: 18%, 1.68 g from milk source). One packet was given daily for 180 d. Counseling on continued breastfeeding and optimal infant-care practices was provided to all. Results We enrolled 1548 infants (high-protein: n  = 512; modest-protein: n  = 519; and no supplement: n  = 517). Compared with the no supplement group, there was an improvement in LAZ [adjusted mean difference (MD): 0.08; 95% CI: 0.01, 0.15], weight-for-age z score (MD: 0.12; 95% CI: 0.06, 0.19), weight-for-length z score (MD: 0.11; 95% CI: 0.02, 0.19), and midupper arm circumference z score (MD: 0.10; 95% CI: 0.02, 0.18) in the high-protein group at 12 mo of age. No significant differences for these anthropometric indicators were noted between the modest-protein and no supplement groups or between the high- and modest-protein groups. Conclusions Cereal mixes with higher amounts of milk-based protein and MMN may lead to improvement in linear growth and other anthropometric indexes in infants, compared with no supplementation. This trial was registered at ctri.nic.in as CTRI/2018/04/012932. [ABSTRACT FROM AUTHOR]

Background Although dietary guidelines recommend that vegetables and fruits make up half the diet, it is unclear whether serving vegetables and fruits in larger portions will have sustained effects on children's intake over multiple days. Objectives This study tested the effects on children's intake of 2 strategies for increasing the proportion of vegetables and fruits: either adding or substituting extra portions as side dishes at meals and snacks over 5 d. Methods In a cluster-randomized crossover design with 3 periods, we provided all meals and snacks for 5 d to 53 children aged 3–5 y in classrooms in their childcare centers. In the Control condition, we served typical portions for all food groups. In the Addition condition we increased portions of low-energy-dense vegetables and fruits by 50%, and in the Substitution condition we increased portions of vegetables and fruits by 50% and also reduced portions of other foods by an equivalent weight. Results For vegetables, the Addition strategy increased daily intake compared with Control by 24% (mean ± SEM = 12 ± 3 g/d; P = 0.0002), and the Substitution strategy increased intake compared with Control by 41% (22 ± 3 g/d; P < 0.0001). For fruits, consumption increased by similar amounts: Addition by 33% (60 ± 6 g/d) and Substitution by 38% (69 ± 8 g/d; both P < 0.0001). Both strategies increased vegetable and fruit intakes compared with Control across all 5 days (all P < 0.004), although the increase in fruit consumption with Addition declined over time (P < 0.0001). Daily energy intake compared with Control increased by 5% with Addition (57 ± 17 kcal; P = 0.001) but decreased by 6% with Substitution (−64 ± 21 kcal; P = 0.004). Conclusions Both the Addition and Substitution strategies promoted increases in vegetable and fruit intake over 5 d in preschool children. When excess energy intake is a concern, substituting vegetables and fruits for other foods is a better option than simply serving more. This trial was registered at http://www.clinicaltrials.gov as NCT03242863 (https://clinicaltrials.gov/ct2/show/NCT03242863), where the protocol is available. [ABSTRACT FROM AUTHOR]

Background Dietary habits formed in early childhood can track into later life with important impacts on health. Food-based dietary guidelines (FBDGs) may have a role in improving population health but are lacking for young children. Objectives We aimed to establish a protocol for addressing nutrient shortfalls in 1- to 5-y-old children (12–60 mo) using diet modeling in a population-based sample. Methods Secondary analysis of 2010–2011 Irish National Pre-School Nutrition Survey data (n  = 500) was conducted to identify typical food consumption patterns in 1- to 5-y-olds. Nutrient intakes were assessed against dietary reference values [European Food Safety Authority (EFSA) and Institute of Medicine (IOM)]. To address nutrient shortfalls using diet modeling, 4-d food patterns were developed to assess different milk-feeding scenarios (human milk, whole or low-fat cow milk, and fortified milks) within energy requirement ranges aligned with the WHO growth standards. FBDGs to address nutrient shortfalls were established based on 120 food patterns. Results Current mean dietary intakes for the majority of 1- to 5-y-olds failed to meet reference values (EFSA) for vitamin D (≤100%), vitamin E (≤88%), DHA (22:6n–3) + EPA (20:5n–3) (IOM; ≤82%), and fiber (≤63%), whereas free sugars intakes exceeded recommendations of <10% energy (E) for 48% of 1- to 3-y-olds and 75% of 4- to 5-y-olds. "Human milk + Cow milk" was the only milk-feeding scenario modeled that predicted sufficient DHA + EPA among 1- to 3-y-olds. Vitamin D shortfalls were not correctable in any milk-feeding scenario, even with supplementation (5 µg/d), apart from the "Follow-up Formula + Fortified drink" scenario in 1- to 3-y-olds (albeit free sugars intakes were estimated at 12%E compared with ≤5%E as provided by other scenarios). Iron and vitamin E shortfalls were most prevalent in scenarios for 1- to 3-y-olds at ≤25th growth percentile. Conclusions Using WHO growth standards and international reference values, this study provides a protocol for addressing nutrient shortfalls among 1- to 5-y-olds, which could be applied in country-specific population health. [ABSTRACT FROM AUTHOR]

Background Evidence is emerging that interdaily meal pattern variability potentially affects response such as thermic effect of food (TEF), macronutrient metabolism, and appetite. Objectives To investigate the effect of irregular meal pattern on TEF, glucose, insulin, lipid profile, and appetite regulation in women who are overweight or with obesity and confirmed insulin resistance. Design In a randomized crossover trial, 9 women [mean ± SD BMI (in kg/m2): 33.3 ± 3.1] with confirmed insulin resistance consumed a regular (14 d; 6 meals/d) and an irregular (14 d; 3–9 meals/d) meal pattern separated by a 14-d washout interval. Identical foods were provided during the interventions, and at the start and end of each meal pattern, participants attended the laboratory after an overnight fast. Energy expenditure, glucose, insulin, lipids, adiponectin, leptin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin were measured at baseline and for 3 h after consumption of a test drink, after which an ad libitum test meal was offered. Subjective appetite ratings were recorded before and after the test drink, after the ad libitum meal, and during the intervention. Continuous interstitial glucose monitoring was undertaken for 7 consecutive days during each intervention. Results TEF (over 3 h) was significantly lower postirregular intervention compared with postregular (97.7 ± 19.2 kJ*3 h in postregular visit and 76.7 ± 35.2 kJ*3 h in postirregular visit, paired t test, P = 0.048). Differences in HOMA-IR between the 2 interventions (3.3 ± 1.7 and 3.6 ± 1.6 in postregular and postirregular meal pattern, respectively) were not significant. Net incremental AUC for GLP-1 concentrations (over 3 h) for the postregular meal pattern were higher (864.9 ± 456.1 pmol/L*3 h) than the postirregular meal pattern (487.6 ± 271.7 pmol/L*3 h, paired t test, P = 0.005). Conclusions Following a 14-d period of an irregular meal pattern, TEF was significantly less than following a regular meal pattern, potentially compromising weight management if sustained long term. This study was registered at www.clinicaltrials.gov as NCT02582606. [ABSTRACT FROM AUTHOR]

Background Maternal nutrition is associated with epigenetic and cardiometabolic risk factors in offspring. Research in humans has primarily focused on assessing the impact of individual nutrients. Objectives We sought to assess the collective impact of maternal dietary MUFAs, PUFAs, and SFAs on epigenetic aging and cardiometabolic risk markers in healthy newborn infants using a geometric framework approach. Methods Body fatness (n  = 162), aortic intima–media thickness (aIMT; n  = 131), heart rate variability (n  = 118), and epigenetic age acceleration (n  = 124) were assessed in newborn infants. Maternal dietary intake was cross-sectionally assessed in the immediate postpartum period via a validated 80-item self-administered FFQ. Generalized additive models were used to explore interactive associations of nutrient intake, with results visualized as response surfaces. Results After adjustment for total energy intake, maternal age, gestational age, and sex there was a 3-way interactive association of MUFAs, PUFAs, and SFAs (P  = 0.001) with newborn epigenetic aging. This suggests that the nature of each fat class association depends upon one another. Response surfaces revealed MUFAs were positively associated with newborn epigenetic age acceleration only at proportionately lower intakes of SFAs or PUFAs. We also demonstrate a potential beneficial association of omega-3 (n–3) PUFAs with newborn epigenetic age acceleration (P  = 0.008). There was no significant association of fat class with newborn aIMT, heart rate variability, or body fatness. Conclusions In this study, we demonstrated an association between maternal dietary fat class composition and epigenetic aging in newborns. Future research should consider other characteristics such as the source of maternal dietary fatty acids. [ABSTRACT FROM AUTHOR]

Background Accumulating evidence links ultra-processed foods to poor diet quality and chronic diseases. Understanding dietary trends is essential to inform priorities and policies to improve diet quality and prevent diet-related chronic diseases. Data are lacking, however, for trends in ultra-processed food intake. Objectives We examined US secular trends in food consumption according to processing level from 2001 to 2018. Methods We analyzed dietary data collected by 24-h recalls from adult participants (aged >19 y; N   = 40,937) in 9 cross-sectional waves of the NHANES (2001–2002 to 2017–2018). We calculated participants' intake of minimally processed foods, processed culinary ingredients, processed foods, and ultra-processed foods as the relative contribution to daily energy intake (%kcal) using the NOVA framework. Trends analyses were performed using linear regression, testing for linear trends by modeling the 9 surveys as an ordinal independent variable. Models were adjusted for age, sex, race/ethnicity, education level, and income. Consumption trends were reported for the full sample and stratified by sex, age groups, race/ethnicity, education level, and income level. Results Adjusting for changes in population characteristics, the consumption of ultra-processed foods increased among all US adults from 2001–2002 to 2017–2018 (from 53.5 to 57.0 %kcal; P -trend < 0.001). The trend was consistent among all sociodemographic subgroups, except Hispanics, in stratified analyses. In contrast, the consumption of minimally processed foods decreased significantly over the study period (from 32.7 to 27.4 %kcal; P -trend < 0.001) and across all sociodemographic strata. The consumption of processed culinary ingredients increased from 3.9 to 5.4 %kcal (P -trend < 0.001), whereas the intake of processed foods remained stable at ∼10 %kcal throughout the study period (P -trend = 0.052). Conclusions The current findings highlight the high consumption of ultra-processed foods in all parts of the US population and demonstrate that intake has continuously increased in the majority of the population in the past 2 decades. [ABSTRACT FROM AUTHOR]

Background Diet is one of the modifiable risk factors for cognitive decline. However, studies on dietary protein intake and cognitive decline have remained limited and inconclusive. Objectives In this study, we aimed to investigate the associations between long-term dietary protein intake and subsequent subjective cognitive decline (SCD). Methods We included 49,493 women from the Nurses' Health Study (NHS) (1984–2006) and 27,842 men from the Health Professionals Follow-up Study (HPFS) (1986–2002). For the NHS, average dietary intake was calculated from 7 repeated semi-quantitative FFQs (SFFQs), and SCD was assessed in 2012 and 2014. For the HPFS, average dietary intake was calculated from 5 repeated SFFQs, and SCD was assessed in 2008 and 2012. Poisson regression was used to examine the associations between dietary protein, amino acids, and various protein food sources with subsequent SCD. Results Higher protein intake compared with total carbohydrates was associated with lower odds of SCD. When substituting 5% energy from protein for the equivalent percentage of energy from total carbohydrates, the pooled multivariable-adjusted ORs (95% CIs) were 0.89 (0.85, 0.94) for total protein, 0.89 (0.84, 0.94) for animal protein, and 0.74 (0.62, 0.88) for plant protein. When substituting 5% of energy from animal protein with plant protein, the OR was 0.84 (95% CI: 0.72, 0.97). For protein food sources, higher intakes of beans/legumes, fish, and lean poultry were significantly associated with lower odds of SCD, but higher intake of hotdogs was associated with higher odds of SCD. Conclusions Higher protein intake was associated with lower odds of SCD when compared isocalorically with carbohydrate. Plant protein sources were also associated with lower odds when compared with animal protein sources. Our findings suggest that adequate protein intake, and choices of protein sources could play a role in the maintenance of cognition and should be studied further. [ABSTRACT FROM AUTHOR]

Background Four models are commonly used to adjust for energy intake when estimating the causal effect of a dietary component on an outcome: 1) the "standard model" adjusts for total energy intake, 2) the "energy partition model" adjusts for remaining energy intake, 3) the "nutrient density model" rescales the exposure as a proportion of total energy, and 4) the "residual model" indirectly adjusts for total energy by using a residual. It remains underappreciated that each approach evaluates a different estimand and only partially accounts for confounding by common dietary causes. Objectives We aimed to clarify the implied causal estimand and interpretation of each model and evaluate their performance in reducing dietary confounding. Methods Semiparametric directed acyclic graphs and Monte Carlo simulations were used to identify the estimands and interpretations implied by each model and explore their performance in the absence or presence of dietary confounding. Results The "standard model" and the mathematically identical "residual model" estimate the average relative causal effect (i.e. a "substitution" effect) but provide biased estimates even in the absence of confounding. The "energy partition model" estimates the total causal effect but only provides unbiased estimates in the absence of confounding or when all other nutrients have equal effects on the outcome. The "nutrient density model" has an obscure interpretation but attempts to estimate the average relative causal effect rescaled as a proportion of total energy. Accurate estimates of both the total and average relative causal effects may instead be derived by simultaneously adjusting for all dietary components, an approach we term the "all-components model." Conclusions Lack of awareness of the estimand differences and accuracy of the 4 modeling approaches may explain some of the apparent heterogeneity among existing nutritional studies. This raises serious questions regarding the validity of meta-analyses where different estimands have been inappropriately pooled. [ABSTRACT FROM AUTHOR]

Background Malnutrition of inpatients is often overlooked and remains a serious concern. However, there are few studies on the relations between infused energy and amino acid intakes and clinical outcomes in older patients on parenteral nutrition. Objectives We aimed to determine the short-term outcomes of infused energy and amino acid intakes in older patients receiving parenteral nutrition. Methods We conducted a retrospective observational study using a national inpatient database covering >1000 hospitals in Japan. Participants were those who underwent central venous (CV) port insertion between 2011 and 2016, were aged ≥65 y, and did not have cancer. Based on the types and amounts of products used for enteral feeding and intravenous feeding on postoperative day (POD) 7 after CV port insertion, the infused energy and amino acid intakes were estimated. The primary end point was mortality on POD 90. Multivariable logistic regression was performed to investigate the relations of infused energy and amino acid intakes with mortality on POD 90. Results A total of 10,153 patients aged ≥65 y who underwent CV port insertion were included. The mortality rates at 90 d after central venous port insertion were 14.9% and 14.0% (risk difference, 0.9%; 95% CI: –0.5%, 2.3%; P  = 0.216) with infused energy intakes <20 and ≥20 kcal/kg, respectively, and 15.4% and 13.2% (risk difference, 2.2%; 95% CI: 0.9%, 3.6%; P  = 0.001) with infused amino acid intakes <0.8 and ≥0.8 g/kg, respectively. The differences were retained after adjustment for multiple variables including hospital, age, sex, BMI, emergency admission, and 27 major underlying diseases. The OR for the ≥0.8-g/kg group compared with the <0.8-g/kg group was 0.87 (95% CI: 0.77, 0.99; P  = 0.028). Conclusions A positive relation between infused amino acid intake and mortality was found in older patients receiving parenteral nutrition. [ABSTRACT FROM AUTHOR]

Background The associations between nut consumption and cancer risk have not been extensively investigated. Objectives We aimed to examine the associations between nut consumption, especially specific types of nuts (peanut, tree nut, walnut, and tree nut other than walnut), and cancer risk. Methods Nut consumption was assessed by FFQ at baseline and updated every 2–4 y in the Nurses' Health Study (1980–2014), the Nurses' Health Study II (1991–2015), and the Health Professionals Follow-up Study (1986–2018). We examined the associations between the intake of total and specific types of nuts and risk of total cancer and common cancers, including lung, colorectal, breast, bladder, and aggressive prostate cancer. Cox proportional-hazards models were used to obtain the HRs and 95% CIs in each cohort as well as pooled. Results During 5,873,671 person-years of follow-up in 180,832 women and 45,560 men, we documented 44,561 incident cancer cases. As compared with nonconsumers, the pooled multivariable HRs of total nut consumption for ≥5 times/wk were 0.99 (95% CI: 0.94, 1.04; P -trend = 0.54) for total cancer, 0.88 (95% CI: 0.74, 1.04; P -trend = 0.18) for lung cancer, 1.07 (95% CI: 0.92, 1.26; P -trend = 0.89) for colorectal cancer, 0.90 (95% CI: 0.71, 1.14; P -trend = 0.65) for bladder cancer, 0.96 (95% CI: 0.85, 1.08; P -trend = 0.36) for breast cancer, and 1.18 (95% CI: 0.92, 1.51; P -trend = 0.52) for aggressive prostate cancer Conclusions In 3 large prospective cohorts, frequent nut consumption was not associated with risk of total cancer and common individual cancers. [ABSTRACT FROM AUTHOR]

Background Effects of soy foods on cerebral blood flow (CBF)—a marker of cerebrovascular function—may contribute to the beneficial effects of plant-based diets on cognitive performance. Objectives We aimed to investigate longer-term effects of soy nut consumption on CBF in older adults. Changes in 3 different domains of cognitive performance were also studied. Methods Twenty-three healthy participants (age: 60–70 y; BMI: 20–30 kg/m2) participated in a randomized, controlled, single-blinded crossover trial with an intervention (67 g/d of soy nuts providing ∼25.5 g protein and 174 mg isoflavones) and control period (no nuts) of 16 wk, separated by an 8-wk washout period. Adults followed the Dutch food-based dietary guidelines. At the end of each period, CBF was assessed with arterial spin labeling MRI. Psychomotor speed, executive function, and memory were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results No serious adverse events were reported, and soy nut intake was well tolerated. Body weights remained stable during the study. Serum isoflavone concentrations increased (daidzein mean difference ± SD: 128 ± 113 ng/mL, P  < 0.001; genistein: 454 ± 256 ng/mL, P  < 0.001), indicating excellent compliance. Regional CBF increased in 4 brain clusters located in the left occipital and temporal lobes (mean ± SD increase: 11.1 ± 12.4 mL · 100 g−1 · min−1, volume: 11,296 mm3, P  < 0.001), bilateral occipital lobe (12.1 ± 15.0 mL · 100 g−1 · min−1, volume: 2632 mm3, P  = 0.002), right occipital and parietal lobes (12.7 ± 14.3 mL · 100 g−1 · min−1, volume: 2280 mm3, P  = 0.005), and left frontal lobe (12.4 ± 14.5 mL · 100 g−1 · min−1, volume: 2120 mm3, P  = 0.009) which is part of the ventral network. These 4 regions are involved in psychomotor speed performance, which improved as the movement time reduced by (mean ± SD) 20 ± 37 ms (P  = 0.005). Executive function and memory did not change. Conclusions Longer-term soy nut consumption may improve cerebrovascular function of older adults, because regional CBF increased. Effects may underlie observed improvements in psychomotor speed. This trial was registered at clinicaltrials.gov as NCT03627637. [ABSTRACT FROM AUTHOR]

Background Intake of a single meal containing herbs and spices attenuates postprandial lipemia, hyperglycemia, and oxidative stress, and improves endothelial function. There has been limited investigation of the effect of longer-term intake of mixed herbs and spices on risk factors for cardiometabolic diseases. Objectives The objective was to assess the effect of an average American diet containing herbs and spices at 0.5 (low-spice diet; LSD), 3.3 (moderate-spice diet; MSD), and 6.6 (high-spice diet; HSD) g · d−1 · 2100 kcal−1 on lipids and lipoproteins as well as other risk factors for cardiometabolic diseases in at-risk adults. Methods A 3-period, randomized, crossover, controlled-feeding study with 71 participants was conducted at the Pennsylvania State University. Each diet was consumed for 4 wk with a minimum 2-wk washout period. Outcomes were assessed at baseline and the end of each diet period. Results No between-diet effects were observed for LDL cholesterol, the primary outcome. Between-diet differences were observed for mean 24-h systolic (P  = 0.02) and diastolic (P  = 0.005) ambulatory blood pressure. The HSD lowered mean 24-h systolic blood pressure compared with the MSD (−1.9 mm Hg; 95% CI: −3.6, −0.2 mm Hg; P  = 0.02); the difference between the HSD and LSD was not statistically significant (−1.6 mm Hg; 95% CI: −3.3, 0.04 mm Hg; P  = 0.058). The HSD lowered mean 24-h diastolic blood pressure compared with the LSD (−1.5 mm Hg; 95% CI: −2.5, −0.4 mm Hg; P  = 0.003). No differences were detected between the LSD and MSD. No between-diet effects were observed for clinic-measured blood pressure, markers of glycemia, or vascular function. Conclusions In the context of a suboptimal US-style diet, addition of a relatively high culinary dosage of mixed herbs and spices (6.6 g · d−1 · 2100 kcal−1) tended to improve 24-h blood pressure after 4 wk, compared with lower dosages (0.5 and 3.3 g · d−1 · 2100 kcal−1), in adults at elevated risk of cardiometabolic diseases. This trial was registered at clinicaltrials.gov as NCT03064932. [ABSTRACT FROM AUTHOR]

Background Limited evidence supports the common public health guideline that children >2 y of age should consume dairy with reduced fat content. Objectives We aimed to investigate the effects of whole-fat compared with reduced-fat dairy intake on measures of adiposity and biomarkers of cardiometabolic risk in healthy 4- to 6-y-old children. Methods The Milky Way Study enrolled 49 children (mean ± SD age: 5.2 ± 0.9 y; 47% girls) who were habitual consumers of whole-fat dairy, then randomly assigned them in a double-blind fashion to remain on whole-fat dairy or switch their dairy consumption to reduced-fat products for 3 mo. Primary endpoints included measures of adiposity, body composition, blood pressure, fasting serum lipids, blood glucose, glycated hemoglobin (HbA1c), and C-reactive protein (CRP) and were assessed at baseline and study end. Pre- and postintervention results were compared using linear mixed models, adjusted for growth, age, and sex. Results Dairy fat intake was reduced by an adjusted (mean ± SEM) 12.9 ± 4.1 g/d in the reduced-fat compared with the whole-fat dairy group (95% CI: –21.2, –4.6 g/d; P  = 0.003), whereas dietary energy intakes remained similar (P  = 0.936). We found no significant differential changes between dairy groups in any measure of adiposity, body composition, blood pressure, or fasting serum lipids, glucose, HbA1c, and CRP. Conclusions Our results suggest that although changing from whole-fat to reduced-fat dairy products does reduce dairy fat intake, it does not result in changes to markers of adiposity or cardiometabolic disease risk in healthy children. This trial was registered at www.anzctr.org.au as ACTRN12616001642471. [ABSTRACT FROM AUTHOR]

Background Vitamin D and dairy protein may stimulate bone mineralization and linear growth in children, but previous studies show inconsistent results and have not examined their combined effects. Objectives To investigate combined and separate effects of vitamin D supplementation and high-protein (HP) compared with normal-protein (NP) yogurt intake on children's bone mineralization and linear growth. Methods In a 2 × 2–factorial trial, 200 healthy, 6- to 8-year-old, Danish, children with light skin (55°N) were randomized to 20 µg/d vitamin D3 or placebo and to substitute 260 g/d dairy with HP (10 g protein/100 g) or NP (3.5 g protein/100 g) yogurt for 24 weeks during an extended winter. Outcomes were total body less head (TBLH) and lumbar spine bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) by dual-energy X-ray absorptiometry, height, and biomarkers of bone turnover and growth. The primary outcome was TBLH BMD. Results In total, 184 children (92%) completed the study. The baseline serum 25-hydroxyvitamin D was 80.8 ± 17.2 nmol/L, which increased by 7.2 ± 14.1 nmol/L and decreased by 32.3 ± 17.5 nmol/L with vitamin D and placebo, respectively. The baseline protein intake was 15.4 ± 2.4 energy percentage (E%), which increased to 18.3 ± 3.4 E% with HP. There were no vitamin D–yogurt interactions and no main effects of either intervention on TBLH BMD. However, vitamin D supplementation increased lumbar spine BMD and TBLH BMC compared to placebo, whereas HP groups showed lower increments in lumbar spine BMD, TBLH BMC and BA, and plasma osteocalcin compared to NP groups. Height, growth factors, and parathyroid hormone levels were unaffected. Conclusions Although there were no effects on whole-body BMD, vitamin D increased bone mass and spinal BMD, whereas high compared with normal dairy protein intake had smaller incremental effects on these outcomes. This supports a recommended vitamin D intake of around 20 µg/d during winter but not use of HP dairy products for improved bone mineralization among healthy, well-nourished children. This trial was registered at clinicaltrials.gov as NCT03956732. [ABSTRACT FROM AUTHOR]

Background Patients with end-stage renal disease (ESRD) undergoing hemodialysis experience a rapid decline in skeletal muscle mass and strength. Hemodialysis removes amino acids (AAs) from the circulation, thereby lowering plasma AA concentrations and stimulating proteolysis. Objectives In the present study, we evaluate the impact of intradialytic protein ingestion at rest and following exercise on AA removal and plasma AA availability in patients with ESRD. Methods Ten patients (age: 65 ± 16 y, male/female: 8/2, BMI: 24.2 ± 4.8 kg/m2, serum albumin: 3.4 ± 0.3 g/dL) with ESRD undergoing hemodialysis participated in this randomized controlled crossover trial. During 4 hemodialysis sessions, patients were assigned to ingest 40 g protein or a placebo 60 min after initiation, both at rest (PRO and PLA, respectively) and following exercise (PRO + EX and PLA + EX, respectively). Spent dialysate and blood samples were collected every 30 min throughout hemodialysis to assess AA removal and plasma AA availability. Results Plasma AA concentrations declined by 26.1 ± 4.5% within 30 min after hemodialysis initiation during all interventions (P  < 0.001, η2p  > 0.79). Protein ingestion, but not intradialytic exercise, increased AA removal throughout hemodialysis (9.8 ± 2.0, 10.2 ± 1.6, 16.7 ± 2.2, and 17.3 ± 2.3 g during PLA, PLA + EX, PRO, and PRO + EX interventions, respectively; protein effect P  < 0.001, η2p  = 0.97; exercise effect P  = 0.32, η2p  = 0.11). Protein ingestion increased plasma AA concentrations until the end of hemodialysis, whereas placebo ingestion resulted in decreased plasma AA concentrations (time effect P  < 0.001, η2p  > 0.84). Plasma AA availability (incremental AUC) was greater during PRO and PRO + EX interventions (49 ± 87 and 70 ± 34 mmol/L/240 min, respectively) compared with PLA and PLA + EX interventions (–227 ± 54 and –208 ± 68 mmol/L/240 min, respectively; protein effect P  < 0.001, η2p  = 0.98; exercise effect P  = 0.21, η2p  = 0.16). Conclusions Protein ingestion during hemodialysis compensates for AA removal and increases plasma AA availability both at rest and during recovery from intradialytic exercise. Intradialytic exercise does not compromise AA removal or reduce plasma AA availability during hemodialysis in a postabsorptive or postprandial state. [ABSTRACT FROM AUTHOR]

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body—resulting from the hormonal responses to a high-glycemic-load diet—drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence. [ABSTRACT FROM AUTHOR]

Background Classical risk factors, such as fasting cholesterol, blood pressure (BP), and diabetes status are used today to predict the risk of developing cardiovascular disease (CVD). However, accurate prediction remains limited, particularly in low-risk groups such as women and younger individuals. Growing evidence suggests that biomarker concentrations following consumption of a meal challenge are better and earlier predictors of disease development than biomarker concentrations. Objective To test the hypothesis that postprandial responses of circulating biomarkers differ between healthy subjects with and without subclinical atherosclerosis (SA) in an Asian population at low risk of coronary artery disease (CAD). Methods One hundred healthy Chinese subjects (46 women, 54 men) completed the study. Subjects consumed a mixed-meal test and 164 blood biomarkers were analyzed over 6 h by using a combination of chemical and NMR techniques. Models were trained using different methodologies (including logistic regression, elastic net, random forest, sparse partial least square) on a random 75% subset of the data, and their performance was evaluated on the remaining 25%. Results We found that models based on baseline clinical parameters or fasting biomarkers could not reliably predict SA. By contrast, an omics model based on magnitude and timing of postprandial biomarkers achieved high performance [receiving operating characteristic (ROC) AUC: 91%; 95% CI: 77, 100). Investigation of key features of this model enabled derivation of a considerably simpler model, solely based on postprandial BP and age, with excellent performance (AUC: 91%; 95% CI: 78, 100). Conclusion We report a novel model to detect SA based on postprandial BP and age in a population of Asian subjects at low risk of CAD. The use of this model in large-scale CVD prevention programs should be explored. This trial was registered at ClinicalTrials.gov as NCT03531879. [ABSTRACT FROM AUTHOR]

Background Both diet and familial factors have a major role in the development of cardiovascular disease (CVD). However, it remains unclear whether familial predisposition to CVD modifies the association between dietary factors and CVD. Objectives The aim was to assess whether the association between diet and CVD varies with familial predisposition to CVD. Methods In this prospective cohort of the UK Biobank, 462,155 CVD-free participants were included in 2006–2010 and followed for CVD incidence until 2020. Food intake was measured using a short food-frequency questionnaire. Familial predisposition was measured by self-reported family history of CVD and by polygenic risk score (PRS) for CVD based on summary statistics of independent genome-wide association studies. Results During a median follow-up of 11.2 y, 46,164 incident CVD cases were identified. A moderately higher risk of CVD was associated with more frequent processed-meat consumption, with an adjusted HR of 1.07 (95% CI: 1.03, 1.11; highest vs. lowest level). Conversely, intakes of fish, cheese, vegetables, and fruit were each associated with reduced CVD risk [HR (95% CI): 0.92 (0.89, 0.96), 0.90 (0.86, 0.94), 0.98 (0.95, 1.00), and 0.93 (0.89, 0.96), respectively]. Stratification analyses by family history of CVD and by PRS for CVD revealed an inverse association between CVD and intakes of fish and cheese, for both subgroups with and without a familial predisposition to CVD. Notably, while the association between processed-meat intake and CVD was restricted to individuals with a familial predisposition to CVD [e.g. HR: 1.11 (1.05, 1.16) and 1.03 (0.97, 1.10) for with and without a family history, respectively, P- interaction < 0.001], the risk reduction of CVD associated with vegetable and fruit intake was only noted among participants without a CVD familial predisposition [e.g. HR for fruit consumption: 1.00 (0.97, 1.03) and 0.91 (0.87, 0.95), respectively, P  < 0.001]. Conclusions Familial factors modify the association between diet and CVD, underscoring the need for personalized dietary guidelines for CVD prevention. [ABSTRACT FROM AUTHOR]

Background To guide the transformation of food systems to provide for healthy and sustainable diets, countries need to assess their current diet and food supply in comparison to nutrition, health, affordability, and environmental goals. Objectives We sought to compare Indonesia's food utilization to diets optimized for nutritional value and cost and to diets that are increasingly plant-based in order to meet further health and environmental goals, including the EAT-Lancet planetary health diet, to explore whether multiple goals could be achieved simultaneously. Methods We compared 13 dietary scenarios (2 current, 7 optimized, 3 increasingly plant-based, 1 EAT-Lancet) for nutrient content, cost, greenhouse gas emissions (GHGe), and water footprints, using the FAO food balance sheet, Indonesia Household Income and Expenditure Survey household food expenditure, food composition, life cycle assessment, food losses, and trade data. Results The diversity of modeled scenarios was higher than that of current consumption, reflecting nutritional deficiencies underlying Indonesia's burden of different forms of malnutrition. Nutrient intake targets were met best by nutrient- and cost-optimized diets, followed by the EAT-Lancet diet. Those diets also had high GHGe, although less than 40% of a scenario in which Indonesia would adopt a typical high-income country's diet. Only the low food chain diet had a GHGe below the 2050 target set by the EAT-Lancet commission. Its nutrient content was comparable to that of a no-dairy diet, slightly above those of fish-and-poultry and current diets, and somewhat below those of the EAT-Lancet diets. To meet nutrient needs, some animal-source foods had to be included. Costs of all except the optimized diets were above the current national average food expenditure. No scenario met all goals simultaneously. Conclusions Indonesia's consumption of rice and unhealthy foods should decrease; food production, trade, and processing should prioritize diversification, (bio)fortification, and limiting environmental impacts; and consumer and institutional demands for healthy, nutritious, and sustainable foods should be stimulated. More granular data and tools are required to develop and assess more detailed scenarios to achieve multiple goals simultaneously. [ABSTRACT FROM AUTHOR]

Background Observed associations of high-protein diets with changes in insulin resistance are inconclusive. Objectives We aimed to assess associations of changes in both reported and estimated protein (PRep; PEst) and energy intake (EIRep; EIEst) with changes in HOMA-IR, glycated hemoglobin (HbA1c), and BMI (in kg/m2), in 1822 decreasing to 833 adults (week 156) with overweight and prediabetes, during the 3-y PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study on weight-loss maintenance. Eating behavior and measurement errors (MEs) of dietary intake were assessed. Thus, observational post hoc analyses were applied. Methods Associations of changes in EIEst, EIRep, PEst, and PRep with changes in HOMA-IR, HbA1c, and BMI were determined by linear mixed-model analysis in 2 arms [high-protein-low-glycemic-index (GI) diet and moderate-protein-moderate-GI diet] of the PREVIEW study. EIEst was derived from energy requirement: total energy expenditure = basal metabolic rate × physical activity level; PEst from urinary nitrogen, and urea. MEs were calculated as [(EIEst − EIRep)/EIEst] × 100% and [(PRep − PEst)/PEst] × 100%. Eating behavior was determined using the Three Factor Eating Questionnaire, examining cognitive dietary restraint, disinhibition, and hunger. Results Increases in PEst and PRep and decreases in EIEst and EIRep were associated with decreases in BMI, but not independently with decreases in HOMA-IR. Increases in PEst and PRep were associated with decreases in HbA1c. PRep and EIRep showed larger changes and stronger associations than PEst and EIEst. Mean ± SD MEs of EIRep and PRep were 38% ± 9% and 14% ± 4%, respectively; ME changes in EIRep and En% PRep were positively associated with changes in BMI and cognitive dietary restraint and inversely with disinhibition and hunger. Conclusions During weight-loss maintenance in adults with prediabetes, increase in protein intake and decrease in energy intake were not associated with decrease in HOMA-IR beyond associations with decrease in BMI. Increases in PEst and PRep were associated with decrease in HbA1c. This trial was registered at clinicaltrials.gov as NCT01777893. [ABSTRACT FROM AUTHOR]

Background The 2019 Canada's Food Guide recommends the consumption of lower fat dairy products to reduce saturated fat (SFA) intakes. Objectives The objective of this study was to assess the impact of such recommendation on SFA intake at a population level in Canada. Methods Analyses were conducted based on dietary intakes from the nationally representative 2015 Canadian Community Health Survey–Nutrition (unweighted n  = 20,103). Dietary intake was assessed using 24-h dietary recalls. Food-based substitution modeling analyses were conducted by replacing all regular-fat dairy products reported by an equal amount of a corresponding lower fat dairy product. Regular-fat dairy products included milks ≥2% fat, cheeses >25% fat, and yogurts ≥2% fat. Corresponding lower fat replacement products were 1% fat milks, 10–25% fat cheeses, and <2% fat yogurts. The National Cancer Institute method was used to account for within-person variation in dietary intakes. Results Replacing all regular-fat dairy products consumed by Canadians (ages ≥2 y) by a corresponding lower fat product reduced the population's SFA intake from 10.8% of total energy intake (%E; 95% CI: 10.7%, 11.0%) to 10.0%E (95% CI: 9.8%, 10.2%). This reduction was mostly attributable to the milk and cheese substitutions (mean SFA reductions of −0.3%E each). The proportion of the population with an SFA intake <10%E was 34.7% (95% CI: 31.2%, 38.2%) before substitution and 51.5% (95% CI: 47.5%, 55.5%) after substitution. Conclusions This food-based substitution modeling analysis suggests that SFA intakes at a population level are slightly reduced if all regular-fat dairy products consumed by Canadians were replaced by a lower fat dairy product. Approximately half of the population would still consume SFAs in excess of 10%E even if all regular-fat dairy consumed were replaced by lower fat dairy. [ABSTRACT FROM AUTHOR]

Background Optimal nutrition in critically ill children involves a complex interplay between the doses, route, and timing of macronutrient delivery. Objectives We aimed to examine the association between the time to achieve delivery of 60% of the prescribed energy and protein targets and clinical outcomes in mechanically ventilated children. Methods We conducted a prospective, observational cohort study of mechanically ventilated children admitted to pediatric intensive care units (PICUs) worldwide. Daily energy and protein delivery were recorded for up to 10 d in the PICU. We calculated "adequacy" as the percentage of the prescribed energy or protein goal delivered by enteral nutrition (EN), parenteral nutrition (PN), and total nutrition (EN + PN). Based on the days required to reach 60% energy or protein adequacy after PICU admission, we categorized patients into 3 groups: early (≤3 d), pragmatic (4 to 7 d), and late (more than 7 d). The primary outcome was 60-d all-cause mortality; secondary outcomes were the incidence of acquired infections and 28-d ventilator-free days (VFDs). Results From 77 participating PICUs, 1844 patients, with a median age of 1.64 y (IQR, 0.47–7.05), were included; the 60-d mortality rate was 5.3% (n  = 97). The average adequacies of delivery via EN + PN was 49% (IQR, 26–70) for energy and 66% (IQR, 44–89) for protein. In multivariable models adjusted for confounders, mortality was significantly lower in patients who achieved targets within 7 d, for energy (adjusted HR, 0.48; 95% CI: 0.28–0.82; P  = 0.007) or protein (adjusted HR, 0.55; 95% CI: 0.33–0.94; P  = 0.027) delivery. There were no clinically significant differences in infections or VFDs between groups. Conclusions Achieving 60% of energy or protein delivery targets within the first 7 d after PICU admission is associated with lower 60-d mortality in mechanically ventilated children, and is not associated with a greater incidence of infections or a reduction in VFDs compared to later achievement of targets. This trial was registered at clinicaltrials.gov as NCT03223038. [ABSTRACT FROM AUTHOR]

Background Prolonged screen time is associated with an increased risk of obesity in adolescents. However, little is known about whether Internet use is also associated with dietary risk factors including consumption of obesogenic foods. Objectives In this study, we examined the associations of leisure-time and study-time Internet use with dietary risk factors in Korean adolescents using nationally representative survey data. Methods We conducted a cross-sectional analysis among 54,416 middle and high school students in the Korea Youth Risk Behavior Web-based Survey 2015. Participants were asked to report the average duration of leisure-time and study-time Internet use, days of skipping breakfast, and frequency of fruit, vegetable, instant noodle, fast-food, chip/cracker, and sugar-sweetened beverage (SSB) intakes. We performed multivariable logistic regression to estimate ORs and 95% CIs for the relations between duration of Internet use and dietary risk factors, accounting for complex survey sampling and adjusting for potential confounders. Results Prolonged leisure-time Internet use (≥241 compared with 1–60 min/d) was associated with higher prevalence of frequent skipping breakfast (OR: 1.39; 95% CI: 1.29, 1.49), low intakes of fruits (OR: 1.27; 95% CI: 1.18, 1.36) and vegetables (OR: 1.43; 95% CI: 1.33, 1.55), and high intakes of instant noodles (OR: 1.87; 95% CI: 1.74, 2.02), fast-food (OR: 1.63; 95% CI: 1.49, 1.78), chips/crackers (OR: 1.37; 95% CI: 1.24, 1.52), and SSBs (OR: 1.63; 95% CI: 1.52, 1.75). Prolonged study-time Internet use (≥121 compared with 1–60 min/d) was inversely associated with prevalence of low fruit (OR: 0.94; 95% CI: 0.88, 1.00) and vegetable (OR: 0.91; 95% CI: 0.85, 0.98) intakes but was positively associated with high intakes of instant noodles (OR: 1.10; 95% CI: 1.03, 1.19) and chips/crackers (OR: 1.13; 95% CI: 1.04, 1.23). The overall associations remained consistent in analyses stratified by sex, grade, region, parental co-residence, perceived household income, perceived stress level, physical activity, and obesity status. Conclusions Our data suggest that prolonged Internet use, particularly during leisure time, is associated with less healthful dietary behaviors in Korean adolescents. [ABSTRACT FROM AUTHOR]