Journal of Nutrition最新文献

Background: Intake of added sugars, such as sucrose, is high globally. In rats, a maternal high-sucrose diet (HSD) from 10 wk before pregnancy to embryonic day (E)19.5 has widespread impacts on maternal, placental, and fetal blood and brain steroid levels, including glucocorticoids, androgens, and aldosterone.

Objectives: This study examined whether maternal HSD during pregnancy alone is sufficient to alter maternal, placental, and fetal steroids.

Methods: Pregnant rats received either a control diet (1% kcal sucrose) or an isocaloric, nutrient-matched HSD (26% kcal sucrose) between E0.5 and 19.5. On E19.5, we collected maternal serum, placenta, fetal blood and brain, and amniotic fluid. We microdissected the placenta and fetal brain and measured 14 steroids using liquid chromatography tandem mass spectrometry (n = 12-15/diet/sex).

Results: Maternal HSD during pregnancy alone did not alter maternal food intake, maternal body mass, and litter size (all P values ≥ 0.29, Student's t-test) but increased the percentage of males in a litter (P = 0.03, Student's t-test). Maternal HSD did not alter steroids in the maternal serum (all P values ≥ 0.21, Student's t-test), placenta [all P values ≥ 0.07, 2-way analysis of variance (ANOVA)], and fetal blood (all P values ≥ 0.13, 2-way ANOVA). Nonetheless, maternal HSD increased testosterone in the fetal nucleus accumbens (P = 0.04, 2-way ANOVA), decreased allopregnanolone in the fetal amygdala (P = 0.01, 2-way ANOVA), and decreased 11-dehydrocorticosterone in the amniotic fluid (P = 0.05, 2-way ANOVA).

Conclusions: Maternal HSD during pregnancy alone does not affect steroid levels in the maternal serum, placenta, or fetal blood of rats, but disrupts testosterone and allopregnanolone levels in critical regions of the fetal brain that regulate reward-seeking and emotion. Thus, although a long-term maternal HSD is necessary for widespread endocrine effects, the fetal brain is sensitive to short-term increases in maternal sucrose consumption during pregnancy.

Background: Prenatal supplementation with the essential nutrient choline improves insulin sensitivity in Wistar rat offspring. Whether these benefits extend to choline's oxidized derivative, betaine, and how they relate to gut microbiota composition and function remains unclear.

Objective: We investigated the effects of prenatal choline or betaine supplementation on metabolic phenotypes and whether gut microbiota features predict functional outcomes in offspring.

Methods: Pregnant Wistar rats (n = 11/group) were fed an AIN-93G diet and randomly assigned to receive either 0.25% choline, 0.25% betaine or no supplementation (control) in their drinking water during pregnancy. One female and one male offspring from each dam (n = 11/group) were weaned to a high-fat diet for 12 weeks. Metabolic measures were analyzed using analysis of variance models, gut microbiota with Analysis of Composition of Microbiomes with Bias Correction, and nested cross-validation was performed to test predictive capacity.

Results: Offspring of choline- and betaine-supplemented dams showed lower body weight (8% in females, p < 0.0001; 7% in males, p < 0.01) and food intake (7% in females, 10% in males; both p < 0.05) compared to control, with variations in fasting blood glucose and plasma glucagon and insulin. Colon GLP-1 concentrations were higher in both supplemented groups (50% in females, 40% in males; p < 0.0001), with betaine exerting 80% higher circulating GLP-1 in males (p < 0.001). Prenatal choline and betaine produced distinct, sex-specific gut microbiota signatures, with 40% higher fecal butyrate concentrations (p < 0.0001). Machine learning identified Akkermansia and Adlercreutzia overlapping with betaine exposure as predictors of fecal butyrate (r = 0.48, p < 0.001) and colon GLP-1 (r = 0.34, p < 0.05).

Conclusions: Prenatal supplementation of choline or betaine enhances features of the glucoregulatory system in offspring in concert with shifts in gut microbiota composition that were predictive of metabolic function.

Background: Previous evidence on the associations of dairy intake with risk of cardiometabolic diseases has been inconsistent with studies showing either inverse, null or positive associations.

Objective: We aimed to assess these associations in China, where dairy consumption level is low and cardiometabolic disease patterns differ from those in the West.

Methods: The China Kadoorie Biobank is a prospective cohort study with ∼512,000 adult participants recruited from ten diverse localities in China during 2004-08. At baseline and periodic resurveys, information on the consumption frequency of major food groups was collected using a validated interviewer-administered laptop-based questionnaire. During approximately 5.4 million person-years of follow-up, 18,306 diabetes, 33,946 ischemic heart diseases (IHD, including 3888 acute myocardial infarction [MI]), 33,670 ischemic stroke (IS), 7191 intracerebral haemorrhage (ICH) cases, and 13,241 cardiovascular deaths were recorded. Cox regression was used to calculate adjusted hazard ratios (HRs) relating dairy intake to cardiometabolic diseases risk.

Results: At baseline, 10.7% of participants regularly consumed (i.e. ≥4 days/week) dairy products, while 70.0% reported never or rare consumption. After adjusting for potential confounders including BMI, dairy consumption was significantly and positively associated with IHD but inversely associated with risks of acute MI, ICH and cardiovascular death, with HRs for regular consumers vs non-consumers being 1.09 (95% CI: 1.06-1.12), 0.88 (0.80-0.98), 0.69 (0.62-0.76) and 0.82 (0.77-0.87), respectively, but not with diabetes and IS. These associations were largely independent of systolic blood pressure.

Conclusions: In Chinese adults, higher dairy consumption was associated with lower risks of acute MI, ICH and cardiovascular death. Future studies are warranted to further elucidate these relationships and their causality.

Background: B vitamins, particularly B-9 and B-12, are essential cofactors in metabolic reactions, including one-carbon (1C) metabolism, which supports growth and overall metabolic function. Although gut bacteria synthesize some B vitamins, this is insufficient to meet host requirements, making dietary intake crucial. Despite their established biochemical roles, their effects on gut homeostasis remain poorly understood.

Objectives: The study investigated the effects of dietary vitamin B-9 and B-12 deficiencies on gut morphology, microbial composition, and their metabolites.

Methods: A total of 48 Sprague-Dawley rats (4-5 wk old, equal sexes) were fed an AIN-93G control diet (n = 16), a vitamin B-9-deficient diet (LB9, n = 16), or a vitamin B-12-deficient diet (LB12, n = 16) for 6 wk. Blood, tissue, and fecal samples were analyzed for serum vitamins, targeted 1C metabolites, histology, gut microbiota, and fecal metabolomics. Data were analyzed using 1-way or 2-way analysis of variance, with significance set at P ≤ 0.05.

Results: Sex-specific differences were observed in body, liver, and brain weights, although no treatment-related effects were detected for these parameters. Serum vitamin B-9 and B-12 concentrations were significantly reduced, with a more pronounced decrease in males in LB9 (9.4 nmol/L) and LB12 (169.6 pmol/L) compared with controls (116.1 nmol/L and 590.0 pmol/L, respectively, P < 0.001). No significant differences were detected in serum 1C metabolites. Histological analysis revealed increased mucosal height in LB12 rats (P = 0.006) and a 68% reduction in acidic mucin content in both deficient groups (P = 0.02). Gut microbial composition and fecal metabolite profiles varied by sex, with notable alterations in bacterial genera including Streptococcus, Lactobacillus, Blautia, Lachnochlostridium, Colidextribacter, and Dorea, as well as metabolites such as hydrocinnamic acid, tryptophan, and N-acetylneuraminic acid.

Conclusions: Dietary vitamin B-9 and B-12 deficiencies induce sex-dependent alterations in gut morphology, microbiota, and metabolite profiles, emphasizing their essential roles in maintaining gastrointestinal and metabolic homeostasis.

Background: Recent research using a data-driven cluster approach has identified 5 discordant subclassifying body mass index (BMI) subgroups, characterized by cardiometabolic biomarkers deviated from those predicted by BMI.

Objectives: This study aimed to investigate the associations of these subgroups with risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and liver-related events (LREs).

Methods: This prospective cohort study included 423,091 participants. The same cluster analysis as reported by Coral et al. was performed to classify subpopulations. Incident MASLD and LREs were determined by electronic health records. Cox proportional hazards models were used to evaluate the hazard ratio (HR) and 95% confidence interval (CI).

Results: Profiles derived from the study were similar to those identified in the work by Coral et al. Individuals with discordantly high liver transaminase [HR (95% CI): 1.72 (1.51, 1.96) for MASLD and 1.42 (1.23, 1.65) for LREs in males and 1.92 (1.61, 2.28) for MASLD and 1.68 (1.32, 2.14) for LREs in females] and hyperglycemia [HR (95% CI): 1.36 (1.06, 1.74) for MASLD and 1.31 (1.01, 1.70) for LREs in males and 1.62 (1.27, 2.08) for MASLD and 1.80 (1.31, 2.47) for LREs in females] had higher risks of liver outcomes compared with the concordant profile. In contrast, we observed a lower risk of MASLD (0.71; 0.60, and 0.84) in females with discordantly high blood pressure relative to their BMI. For discordant adverse lipid profile and discordant inflammatory profile, no significant associations were observed. In addition, the BMI subclassification profiles had better predictive ability among males.

Conclusions: Metabolically distinct BMI subgroups exhibit heterogeneous risks of MASLD and LREs.

Background: Fortification, the addition of essential micronutrients during food processing, reduces mortality and malnutrition.

Objectives: To comprehensively synthesize global evidence on the cost-effectiveness (CE) and economic benefits of food fortification.

Methods: We employed systematic review methodology, searching 6 databases to January 2024. Eligible studies included economic analyses comparing staple food postharvest micronutrient fortification to no fortification. Quality appraisal used Philips' modeling framework. We converted incremental cost-effectiveness ratios (ICERs) to 2022 US$, and synthesized the data overall and by micronutrient. For illustration, findings were also categorized by "hypothetical" CE thresholds based on common example percentages of gross domestic product per capita (GDP pc) per country.

Results: After screening 6425 abstracts, 56 studies in 66 reports were included, reporting >200 analyses. Sixty-three countries were represented, including >40 low- and middle-income economies (LMICs). Most frequent interventions were as follows: vitamin A, folic acid, iron, and iodine added to cereal grains/products (e.g., flours), oils, and condiments (e.g., sugar, salt). Models were heterogeneous and employed various perspectives. Most evaluations (58%; 135/232) had ICERs < $150 per disability-adjusted life year (DALY) averted (or healthy life year gained). We found 87% (201/232) overall were within a hypothetical CE threshold of "50% GDP pc". With an example "35% GDP pc" level among LMICs, 84% (190/227) were estimated to be cost-effective, and 71% (37/52) were < "20% GDP pc" among low-income countries. Additionally, 6 out of 8 cost-utility studies' ICERs were dominant. Moreover, 47 total unique benefit-cost ratios found benefits outweighed costs, median 8·7:1 (range 1·50:1 to 100·6:1).

Conclusions: Food fortification programs are likely cost-effective in the majority of contexts. Although CE evaluations are specific to local factors and methodology, this research can assist with evidence-informed decision-making for global health policy and priority setting, particularly in resource-constrained economies.

Clinical registration: PROSPERO CRD42023493795.

Background: Vitamin D is required for growth and development. However, little is known about dietary intake and status during early childhood.

Objectives: To determine vitamin D intake and status in a group of Canadian toddlers.

Methods: This is a secondary analysis of data from toddlers enrolled in a double-blind randomized controlled trial of fatty acid supplementation, between ages 1y and 2 y in Vancouver (latitude 49°N), Canada. Dietary information was collected using a 3-d food record, and supplement use by questionnaire. Plasma 25-hydroxyvitamin D₃ (25OHD) concentrations were quantified by liquid chromatography-tandem mass spectrometry. Blood sampling was dichotomized by season as winter (September to February) and summer (March to August).

Results: At age 1 y (n = 110) and 2 y (n = 86), the top food sources of vitamin D were dairy (73‒81%), fish (6.8‒14%), and eggs (4.1‒5.5%). Vitamin D-containing supplements were consumed by 43% of the toddlers at age 1 y and 48% at 2 y. Daily median (interquartile range) total vitamin D intakes were 7.9 (4.9‒13) μg at age 1 y and 7.2 (4.8‒14) μg at age 2 y. There was a higher prevalence of inadequate intake (<10 μg/d) in toddlers not using vitamin D supplements at age 1 y (92% compared with 19%) and 2 y (96% compared with 34%). Overall, mean (standard deviation) 25OHD concentrations were 59.9 (17.6) nmol/L at age 1 y (n = 124) and 60.9 (13.6) nmol/L at 2 y (n = 104). The prevalence of low vitamin D status (<50 nmol/L) was 27% at age 1 y and 22% at 2 y. At age 1 y, the prevalence of low vitamin D status was higher in winter (adjusted prevalence 43% compared with 13%; P < 0.001). Total vitamin D intake correlated with 25OHD at both ages (r ∼0.2, P < 0.05).

Conclusions: These findings suggest a high prevalence of inadequate vitamin D intakes in toddlers who do not consume a vitamin D supplement. A national-level surveillance is needed for this important life stage.

Background: Compartmental modeling can provide unique descriptive and quantitative information about the whole-body metabolism of nutrients. Successful application of modeling requires extensive experience with software such as Simulation, Analysis and Modeling (SAAM), which has limited its use in nutrition.

Objectives: Using vitamin A (VA) as an example, we tested the hypothesis that one could successfully model a new set of data using a "master deck" (model input file) developed for another dataset by an experienced modeler.

Methods: We generated retinol kinetic parameters and state variables for 20 theoretical adults with a wide range of VA total body stores (TBS) and simulated plasma retinol tracer response after an oral isotope dose. Using SAAM, we created a master deck to model group mean tracer response and obtained estimates of model parameters, including TBS. Then we replaced the mean data with that for 4 of the theoretical individuals or for a group of previously studied Ghanaian women, adjusted key parameters, if needed, and determined model parameters for comparison with assigned values (theoretical subjects) or published results (Ghanaian women).

Results: Ratios of model-predicted/reference values for TBS ranged from 1.00 to 1.02 for the 4 theoretical subjects and were 1.00 for the Ghanaian women; fitting required only minor adjustments, if any, in the model parameter related to retinol transfer from plasma to liver stores. Using the theoretical data, we also confirmed that, for adults with a wide range of TBS, the best time to apply retinol isotope dilution was at 21-28 d postdosing.

Conclusions: Results indicate that, using a previously published compartmental model and the associated modeling deck, researchers may be able to analyze a new VA kinetics dataset, making minor adjustments in key parameters as needed to allow nonlinear regression analysis. This approach may make compartmental analysis more accessible for VA researchers.

Background: Consuming protein with additional energy as essential amino acid (EAA), and not carbohydrate, has recently been shown to result in greater postexercise muscle protein synthesis (MPS) during energy deficit (DEF). However, the molecular underpinnings governing these changes in MPS are unclear.

Objectives: This study examined the effects of consuming EAA-enriched whey with added EAA (+EAA) or carbohydrate (+CHO) on skeletal muscle microRNA (miRNA) after exercise in energy balance (BAL) and DEF.

Methods: Seventeen adults completed a randomized, double-blind 2-way mixed model study, consuming 5-d of BAL and DEF (-30 ± 3% energy requirements) diets separated by ≥7-d. On day 6 of each condition, volunteers consumed either a +EAA (304 kcal, 56 g protein, 48 g EAA, 17 g carbohydrate, 2 g fat, n = 8) or +CHO (311 kcal, 34 g protein, 24 g EAA, 40 g carbohydrate, 2 g fat, n = 9) drink after 60-min of load carriage (59 ± 4% peak oxygen uptake) and step ups (9 sets × 16 repetitions). miRNA (microarray RT-qPCR) expression was determined at rest (PRE) and 4-h into recovery (REC). Change in MPS (²H₅-phenylalanine; previously reported) was determined during REC.

Results: Three miRNA (miR-194-5p, miR-324-3p, let-7i-5p) increased (P < 0.05, false detection rate < 0.1) from BAL to DEF, regardless of time and treatment. During DEF REC, miR-194-5p was inversely associated with ΔMPS (r = -0.59, P = 0.03). In vitro overexpression of miR-194-5p in C2C12 skeletal muscle cells elicited lower p-mTOR^Ser2448, p-p70S6K^Thr424/421, and p-rpS6^Ser235/236 than CON.

Conclusions: These data provide a molecular basis for postexercise anabolic resistance during DEF. The increase in miR-194-5p from BAL to DEF likely attenuates postexercise MPS by downregulating anabolic signaling, an effect not mediated by consuming additional EAA or carbohydrate. This trial was registered at clinicaltrials.gov as NCT04621175.