Search Results (320)

Background/Objectives: The impact of dietary adherence and formula intake regularity on fat-soluble vitamin status in phenylketonuria (PKU) is uncertain. This study assessed whether vitamin A, D, E, and beta-carotene levels differ by dietary adherence and regularity of Phe-free formula intake. Methods: A cross-sectional study included 98 individuals (age 6–41 years) with vitamin D measurements. In a subgroup of 68 patients, vitamin A, vitamin E, and beta-carotene levels were determined. Vitamin levels were compared between adherent and non-adherent groups and between participants with regular vs. irregular formula intake. A subsequent systematic review and meta-analysis of six studies (from PubMed, Scopus, Web of Science, and Cochrane; searched in August 2025) pooled standardised mean differences (SMDs) using fixed-effects and random-effects models. Results: The cross-sectional results showed higher vitamin D in adherent (35.60 [30.39–41.65] vs. 32.90 [26.50–40.00] ng/mL, p = 0.034) and regular formula consumers (35.97 [30.03–42.28] vs. 30.20 [26.08–35.06] ng/mL, p = 0.002). Beta-carotene was elevated with regular intake (74.40 [56.70–98.45] vs. 53.20 [34.10–68.60] ng/mL, p = 0.003). Meta-analysis confirmed higher vitamin D in adherent individuals (fixed-effects model, SMD = 0.290, 95% CI: 0.004, 0.576, p = 0.047) and regular consumers (fixed-effects model, SMD = 0.750, 95% CI: 0.382, 1.118, p < 0.0001). No differences were observed for vitamin E or beta-carotene. Conclusions: Adherence to diet and regular formula intake is associated with improved vitamin D status, underscoring the critical role of fortified formulas in PKU management. The very low certainty of evidence necessitates further research, especially for the other fat-soluble vitamins. Nonetheless, clinical practice should emphasise support for adherence and ongoing nutritional monitoring. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder in both children and adults. Pediatric MASLD, however, is not simply an early form of adult disease, as it exhibits distinct developmental, histological, and metabolic features. Emerging evidence suggests that these characteristics arise from a complex, multi-hit continuum that begins in utero. Maternal obesity, gestational diabetes, and poor diet quality during pregnancy have been associated with greater hepatic steatosis in offspring, raising the possibility that intrauterine exposure to dyslipidemia, hyperglycemia, and elevated free fatty acid flux may contribute to early hepatic lipid deposition. After birth, feeding behaviors such as a prolonged breastfeeding appear protective, whereas formula feeding, especially high added-sugar formulations, may accelerate rapid weight gain and increase susceptibility to later steatosis. Early childhood diets high in added sugars, saturated fats, and ultra-processed foods may further promote hepatic lipogenesis and inflammation and interact with underlying genetic susceptibility. Given the heterogeneity of available human cohort studies and mechanistic model systems, this narrative review summarizes converging evidence from prenatal, postnatal, and early childhood nutritional exposures and their relationship to offspring hepatic lipid accumulation, emphasizing early-life windows for intervention to reduce the burden of pediatric MASLD. Full article

Objectives: Erhuang Quzhi Formula (EQF) has been used for the treatment of non-alcoholic fatty liver disease (NAFLD). However, its active components and mechanistic basis remain unclear. This study aims to systematically identify the therapeutic material basis of EQF and to elucidate its potential mechanisms of action against NAFLD through an integrated multi-omics strategy. Methods: An integrated strategy combining UPLC-Q-TOF-MS and network pharmacology was applied to characterize serum components of EQF and construct a compound–target network. Core targets were screened and validated by molecular docking. A NAFLD model was established in C57BL/6 mice through high-fat diet feeding. To evaluate the therapeutic effects, mice were treated with EQF and assessed by measurements of serum biochemical parameters, liver histopathology, and glucose tolerance. UPLC-Q-TOF-based lipidomic and metabolomic analyses of liver tissue were conducted to clarify EQF’s regulatory effects on global lipid profiles and endogenous metabolites. Key genes and proteins involved in relevant signaling pathways were verified by RT-qPCR and Western blot. Results: A total of thirty-one prototype compounds were identified in the EQF-containing serum. Network pharmacology analysis predicted that EQF may alleviate NAFLD by acting on core targets such as TNF, JUN, and STAT3. In vivo experiments demonstrated that EQF administration significantly improved liver function, attenuated dyslipidemia, and reduced inflammation in model mice. Furthermore, metabolomic and lipidomic analyses indicated that EQF effectively reversed abnormal glycerophospholipid and sphingolipid levels and restored their metabolic homeostasis. Conclusions: EQF exerts therapeutic effects in a NAFLD mouse model through multi-component, multi-target, and multi-pathway mechanisms, primarily associated with the regulation of lipid metabolism, improvement of liver function, and suppression of inflammatory responses. This study provides mechanistic insights and a pharmacodynamic basis for the future clinical investigation of EQF. Full article

Background/Objectives: Early cow’s milk formula (CMF) exposure in the neonatal period has been proposed as a risk factor for cow’s milk protein allergy (CMPA), although evidence remains inconsistent. This study evaluated the association between CMF use within the first 72 h and later CMPA. Methods: This retrospective study included 106 CMPA infants and 106 controls. CMPA was diagnosed according to ESPGHAN 2024 guidelines using clinical assessment, a 2–4-week elimination diet, and a supervised oral food challenge. Demographic and feeding data were collected, and logistic regression identified independent predictors. Results: Early CMF exposure was more common in the CMPA group (76% vs. 59%; p = 0.006). Multivariate analysis confirmed early CMF exposure as an independent risk factor (aOR: 2.35; 95% CI: 1.18–4.68). A subgroup with CMF intake limited to the first 72 h followed by exclusive breastfeeding was markedly overrepresented among CMPA cases (47% vs. 12%; p < 0.001). Early CMF exposure did not significantly impact IgE versus non-IgE phenotype distribution. Family history of atopy also remained a strong predictor. Conclusions: Early CMF exposure during the first 72 h and family history of atopy were key risk factors for CMPA. Supporting breastfeeding initiation and avoiding unnecessary early CMF supplementation may help reduce CMPA incidence. Full article

Hypoxia-inducible factor-1 (HIF-1) enhances cancer cell survival in hypoxic conditions. The ketogenic diet (KGD), characterized by low-carbohydrate and high-fat intake, has been widely used for epilepsy treatment and reported to have antitumor potential. However, its impact on hypoxic cancer cells remains poorly understood. This study examined the effects of combining the HIF-1α inhibitor YC-1 with the KD formula KetoCal^® on hypoxic hepatocellular carcinoma (HCC) cells. In vitro, HIF-1α knockdown (KD) and scramble control (SC) Hep3B and HepG2 cells were treated with palmitic acid (PA) and/or β-hydroxybutyrate (BOH) to mimic the KGD environment. PA significantly induced cell death and reactive oxygen species (ROS) in hypoxic KD cells, and this effect was further enhanced by BOH. Gene expression analysis indicated that HIF-1 suppresses fatty acid oxidation (FAO) and ketolysis under hypoxia. In vivo, Hep3B cells were implanted into mice fed KetoCal^® with or without YC-1. KetoCal^® elevated serum BOH and free fatty acids (FFAs), suppressed tumor growth, and increased intra-tumoral acetyl-CoA, ROS, and apoptosis in YC-1-treated tumors. These findings suggest that YC-1 combined with KetoCal^® reactivates FAO and ketolysis, promoting acetyl-CoA accumulation and lethal ROS production in hypoxic HCC. This strategy may offer a novel preclinical model for targeting hypoxic tumors. Full article

Background/Objectives: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus that is challenging to treat. Ketogenic diets (KD) are used in patients with refractory epilepsy due to its well-documented efficacy for seizure control. As more individuals with refractory epilepsy are maintained on KD, clinicians are increasingly identifying EoE in this population. Methods: This is a retrospective clinician reported case series collected through a survey of registered dietitians who have managed a patient(s) on KD, who also had EoE, to describe what diet approaches were used. Data was collected on patient demographics, epilepsy diagnosis, feeding methods, diet prior to EoE diagnosis, endoscopy findings, EoE treatment, diet after EoE diagnosis, follow-up endoscopy results, and treatment response. Results: Nine unique cases were reported. In nearly all cases (except one), clinicians implemented dietary modifications following an EoE diagnosis alongside conventional medical therapies. The dietary strategies varied: three received an extensively hydrolyzed whey-based ketogenic formula via tube feeding, two were managed with plant-based ketogenic formulas, while one case each was placed on a complete amino acid protein plus modular ketogenic tube-fed diet, a low-dairy oral KD, and a nut-free oral KD. Only two encountered difficulties with the dietary modifications, whereas the majority reported noticeable improvements in gastrointestinal symptoms. Conclusions: This study describes several dietary approaches used to address EoE in patients following a KD. Limitations include the small and retrospective nature of the study. Further research is needed to understand the long-term efficacy and pathophysiology of these dietary interventions in those with EoE. Full article

Background/Objectives: Worldwide, an estimated 20–30% of infants suffer from infant colic (IC), with excessive crying and unsettled behavior, during the first three months of life. These infants are often referred for a medical evaluation, but the pathogenesis of IC remains poorly understood. The aim of this narrative review is to critically appraise the available literature regarding the relation between IC and cow’s milk allergy (CMA). Methods: A literature search using the search strings cow’s milk allergy [MeSH Terms] OR food allergy [MesH Terms] AND colic [MeSH Terms] OR crying [MeSH Terms], limited to the English language, from inception to 15 June 2025, resulted in the identification of 135 articles. Of these, 18 clinical trials assessed the effect of a cow’s milk elimination diet on IC. Results: The role of CMA in IC in the absence of other allergic manifestations remains uncertain. However, when standard treatment of infant colic has failed and when other allergic symptoms are present, CMA may be considered. A diagnostic elimination diet which includes a 2–4-week trial of maternal cow’s milk elimination in breastfed infants or an extensively hydrolyzed cow’s milk or hydrolyzed rice formula should be performed. If the elimination diet results in a significant decrease in symptoms, reintroduction of cow’s milk protein into the diet is mandatory to fulfill the diagnostic criteria of CMA. Conclusions: Considering the limited current evidence, future research should prioritize large well-designed clinical trials with a focus on investigating CMA in colicky breastfed and formula-fed infants. Full article

Background: Obesity is a disease with high prevalence worldwide, and the accumulation of visceral fat is related to increased cardiovascular risk. The inclusion of polyunsaturated fatty acids (PUFAs) in the diet has been shown to be a promising nutritional strategy. We aimed to examine the associations between PUFAs consumption and visceral adiposity dysfunction, assessed by the visceral adiposity index (VAI). Methods: This cross-sectional study included 697 adults from the SHIP-Brazil cohort. Structured interviews collected sociodemographic, lifestyle, and dietary data. The intake of omega-3, omega-6, EPA, DHA, and EPA + DHA intake assessed through an adapted food frequency questionnaire (FFQ) was categorized into tertiles. Serum lipids were analyzed using the Cobas system, and VAI was calculated by a sex-specific formula and categorized into two groups (low and high VAI, p50), according to sex. Results: Among men, a higher VAI was associated with greater energy intake and higher carbohydrate and fat consumption. Among women, EPA + DHA intake (β = −0.396, 95% CI: −0.639; −0.152, p = 0.001), EPA (β = −0.679, 95% CI: −1.220; −0.138, p = 0.014), and DHA (β = −0.780, 95% CI: −1.207; −0.352, p < 0.001) were negatively associated with VAI, while omega-6 (β = 0.015, 95% CI: 0.003; 0.028, p = 0.017) showed a positive association. No associations were found between saturated and monounsaturated fatty acids and VAI. Conclusions: The EPA + DHA intake, EPA, and DHA intake were inversely associated with VAI in women, but not in men. Omega-6 intake was negatively associated with VAI in men and positively associated with VAI in women. It is important to highlight that, given the cross-sectional design, these associations do not establish temporality or causality. Full article

Under the spatial distribution of water resources, with more water resources in the southern regions and less in the northern regions, and the “north–south grain transport” pattern, calculating the virtual water flow in food trade between provinces in China and analyzing its sustainability is crucial for ensuring the country’s water resources and food security. By considering various products and consumption types, the virtual water flow in inter-provincial grain trade is estimated using the Minimum Transport Cost Method and the Penman-Monteith formula. The sustainability of this virtual water flow is evaluated at the provincial level. (1) The results show that the top three provinces with the largest net virtual water outflow from inter-provincial grain trade are Heilongjiang, Henan, and Anhui, with net outflows of 43.166 billion m³, 18.974 billion m³, and 13.089 billion m³, respectively. The top three provinces with the largest net virtual water inflows are Hebei, Guangxi, and Liaoning, with net inflows of 18.875 billion m³, 10.076 billion m³, and 8.795 billion m³, respectively. (2) The largest inter-provincial virtual water flow occurs from Henan to Hebei (15.06 billion m³), followed by Inner Mongolia to Hunan (9.57 billion m³), and Heilongjiang to Hubei (9.04 billion m³). (3) Overall, the current pattern of virtual water flow in China’s grain trade is sustainable, though several exporting provinces are under greater stress. In the actual scenario, the average water resource pressure index across all provinces is 0.43, 17.31% lower than the average of 0.52 in the scenario without inter-provincial grain trade. Compared with the scenario without inter-provincial grain product trade, in the actual scenario, Heilongjiang, Jilin, and Inner Mongolia show a higher increase in water resource pressure index, with increases of 94.74%, 73.68%, and 48%, respectively; Beijing, Shanghai, and Qinghai show a greater decrease in water resource pressure index, with reductions of 94.64%, 79.41%, and 66.67%, individually. And then, efforts should be made to adjust and optimize the structure of grain production and circulation; provinces with virtual water net outflow (such as Heilongjiang, Henan, Anhui, etc.) need to adjust their grain cultivation types and grain export structures.; provinces with virtual water net inflow (such as Hebei, Guangxi, Liaoning, etc.) can appropriately expand the scale of grain cultivation, while adjusting their diets to reduce the demand for water-intensive grains. Full article

Background: Necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality in very low birthweight (VLBW) infants. Human milk feeding and standardized feeding protocols are protective, but clinical practice varies, particularly in fortifier choice. Whether human milk-derived fortifiers reduce NEC risk compared with cow milk-derived fortifiers remains unclear. Methods: We conducted a systematic state-of-evidence review and meta-analysis, searching PubMed, Web of Science, and Scopus through July 2025. Eligible studies included RCTs and observational cohorts of VLBW infants comparing an exclusive human milk diet (EHMD) including human milk-derived fortifiers to cow milk-derived diets. Two reviewers independently screened and extracted data. Both RCTs and observational studies were included to evaluate consistency of effect estimates across designs and to account for heterogeneity in control group feeding practices. Pooled odds ratios (ORs) with 95% CIs were calculated using a Sidik–Jonkman random-effects model. Sensitivity analyses by study design and exclusion of infant formula from controls were performed. Results: Twenty studies (five RCTs, 15 observational; n = 6794 infants) met inclusion criteria, most enrolling infants born ≤1250 g. Compared with cow milk-containing diets, EHMD was associated with lower odds of Bell Stage ≥ 2 NEC (OR: 0.59; 95% CI: 0.42, 0.81; p < 0.001; n = 4625) and surgical NEC (OR: 0.43; 95% CI: 0.32, 0.58; p < 0.0001; n = 4754). In direct comparisons of fortifier type with a base diet of human milk, estimates suggested lower odds of Bell Stage ≥ 2 NEC by 35% (OR: 0.65; 95% CI: 0.44, 0.97; p = 0.03, n = 2102) and surgical NEC by 49% (OR: 0.51; 95% CI: 0.26, 0.98; p = 0.04; n = 1659) with human milk-derived fortifiers. Effect estimates were generally consistent across study designs, although precision and statistical significance varied. Conclusions: EHMD with human milk-derived fortifiers was associated with lower odds of medical and surgical NEC in VLBW infants, with most evidence from infants born ≤1250 g, reflecting current clinical use in the highest-risk population. Although the number and sample sizes of RCTs remain limited, the consistency of effect estimates across both RCTs and observational studies, together with significance of pooled analyses, strengthens confidence in these findings. Pragmatic and registry-based studies using standardized fortification protocols may provide the most efficient pathway to strengthen the evidence base. Full article

Background/Objectives: Sarcopenia is common in patients with diabetes mellitus. The use of branched-chain amino acids may influence muscle mass. The aim of this study is to evaluate the effect of a diabetes-specific formula enriched with calcium hydroxy-methyl-butyrate (CaHMB) on muscle mass in patients with diabetes and high risk of malnutrition. Methods: A prospective observational study in 95 patients divided into two cohorts of patients with diabetes, treated with a tailored diet, dietary counseling, and diabetes-specific oral nutritional supplements (ONSs) administered between meals: one enriched with CaHMB (CaHMB Diabetes ONS) 44 (46.32%) patients; and another without CaHMB (Diabetes-Specific ONS) 51 (53.68%) patients. Anthropometric parameters, bioimpedance, artificial intelligence (AI)-assisted ultrasound of the rectus femoris muscle (PIIXMED^TM), and handgrip strength were assessed. Evaluations were conducted at baseline and after 3 months. Results: The mean age was 71.05 (10.67) years; 56.8% were male. After three months, both groups increased their nutritional intake with no differences in dietary protein content between groups. The CaHMB group showed a greater increase in muscle mass as measured by ultrasound, both in muscle area (CaHMB ONS: +5.84 (−3.3 ± 21.58)% vs. Diabetes-Specific ONS: −9.34% (−25.78 ± 12.02)%; p < 0.01) and muscle thickness (CaHMB ONS: +9.17 (−4.40 ± 21.05)% vs. Diabetes-Specific ONS −6.30 (−18.57 ± 12.56)%; p < 0.01). The CaHMB ONS group showed a higher likelihood of increased muscle mass compared to the Diabetes-Specific ONS, with an odds ratio (OR) of 9.31 (95%CI: 2.16–40.13) for thickness and 3.96 (95%CI: 1.11–14.13) for area, adjusted for gender, age, serum albumin, and baseline glycated hemoglobin. Conclusions: Supplementation with Ca-HMB in patients with diabetes and high risk of malnutrition showed significant improvements in muscle mass as assessed by AI-assisted ultrasound. Both groups increased nutritional intake, but only the CaHMB group showed specific benefits in muscle parameters. Full article

Background/Objectives: The efficacy of exclusive enteral nutrition (EEN) on the induction of remission of Crohn’s disease (CD) has been demonstrated with different diets (elemental, semi-elemental, and polymeric). A narrative review was conducted to assess the effects of different enteral diets in pediatric CD patients, considering the hypothesis that manipulating the nutritional key ingredients may enhance the clinical efficacy. Methods: An extensive literature search was performed across PubMed, Embase, and the Cochrane Library, covering all records published up to 27 July 2025. Both pediatric and adult studies were considered, and nutritional composition was compared with remission rates. Results: Twelve studies involving patients with active CD treated with EEN were found. Most studies were conducted with polymeric diets (n = 8), which achieved a high remission rate (up to 85%), thus confirming their advantage over other EEN diets. Conclusions: EEN with polymeric diets satisfies the need to revert the acute inflammation in most pediatric CD patients. Polymeric formulas have two advantages: (a) they contain transforming growth factor-β (TGF-β), which exerts anti-inflammatory effects on intestinal epithelial cells, and (b) they have a mixed-fat composition, including saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs) as well medium-chain triglycerides (MCTs), which provides better results than EEN diets enriched with single-fat components. However, pathophysiological evidence shows gut microbiota alterations after EEN begins, despite clinical improvement. So, a potential strategy to enhance the efficacy of polymeric diets may be fiber enrichment. Full article

Background: Phenylketonuria (PKU) is an inherited metabolic disorder that requires early diagnosis and strict phenylalanine (Phe)-restricted diet to prevent neurocognitive impairment. Various infant feeding models have been used to achieve optimal metabolic control during early life. The aim of this study was to compare two different feeding models for infants with classical PKU in terms of metabolic control, growth parameters, micronutrient status, the process of introducing complementary foods, and with a particular focus on sleep quality. Methods: In this prospective observational study, 26 infants with classical PKU were followed for 12 months. Patients were assigned to one of two feeding groups: Group-1 received breast milk and Phe-free formula in alternating feeds, while Group-2 received Phe-free formula followed by breastfeeding until satiety. Blood Phe, micronutrient levels and anthropometric measurements were recorded. Sleep quality was evaluated using the Brief Infant Sleep Questionnaire-Revised (BISQ-R). A structured set of parental questions was used to evaluate their experiences during the complementary feeding period. Results: No statistically significant differences were observed between the groups in terms of blood Phe levels, anthropometric measurements, serum levels of iron, ferritin, vitamin-B12, vitamin-D, and zinc. Complementary feeding tolerance were similar across the groups. The BISQ-R analysis revealed no significant differences between the groups. Conclusions: Both feeding models were equally effective in maintaining metabolic control, supporting normal growth, complementary feeding processes, and preserving sleep quality during infancy. These findings suggest that either approach can be adopted based on the preference of the caregiver and the practicality of the clinical setting. Full article

Background: The primary treatment for inborn errors of metabolism (IEM) involves restricted intake of natural protein. Inadequate diets can lead to an increased risk of inflammation and susceptibility to infections. The Dietary Inflammatory Index (DII) is used to estimate whether a diet has anti-inflammatory or pro-inflammatory properties. This study aimed to investigate the relationship between the inflammatory index score of natural protein-restricted diets used in medical nutrition therapy for IEM intoxication, the anthropometric measurements and nutritional status of affected children. Method: The study included 20 patients (5 organic acidemia, 5 urea cycle disorders, 10 phenylketonuria) and 20 healthy children. Patients followed a natural protein-restricted diet, while the healthy control group maintained their usual dietary habits. Dietary records were collected for both groups, and the DII and macro-micronutrient intakes were calculated. Result: DII scores were similar between the patient and control groups. Anthropometric measurements did not differ significantly between the groups. However, carbohydrate and fat intakes were higher in the patient group compared to the control group (p < 0.05). Additionally, comparative analyses revealed that vitamin B1, C and E, iron, and magnesium intakes were higher in the patient group than in the control group. Conclusions: Children on a natural protein-restricted diet showed growth patterns comparable to their healthy peers. This study demonstrated that nutritional deficiencies can be prevented in amino acid metabolism disorders treated with a natural protein-restricted diet by carefully controlling nutrition with vitamin and mineral-fortified formulas. Full article

Background/Objectives: Dietary treatment in phenylketonuria consists of a phenylalanine-restricted diet supplemented with a phenylalanine-free medical formula (Phe-FF). During the first six months of life, phenylalanine requirements can be met with breast milk (BM) or infant formula (IF). Despite all the benefits breastfeeding confers, it is often discontinued upon diagnosis of phenylketonuria, so more evidence is needed to support it. This study aimed to compare the assessments of nutritional status and metabolic control in infants with hyperphenylalaninemia/phenylketonuria who received BM, IF, or a combination of both as sources of intact protein, in addition to Phe-FF. Methods: A retrospective observational study was conducted in hyperphenylalaninemia/phenylketonuria patients between 0 and 6 months of age. Three groups were compared depending on the source of intact protein ingested: (1) BM + Phe-FF; (2) IF + Phe-FF; (3) mixture of BM and IF (BM + IF + Phe-FF). At each clinic visit, an anthropometric assessment and phenylalanine blood levels were analyzed. Results: 185 nutritional and metabolic assessments were included. The lowest median phenylalanine blood concentration was observed in the BM + Phe-FF group (129 µmol/L, interquartile range [IQR]: 39.5–232.5). In the BM + Phe-FF group all assessments were classified as eutrophic: −0.09 (SD ± 0.78); a statistically significant difference was observed between the BMI Z-Score of BM + Phe-FF and BM + IF-Phe-FF (p = 0.036). No statistically significant differences were observed in length/age Z-Score. Conclusions: Our results indicate that BM is the best option as a source of intact protein for children under 6 months of age with hyperphenylalaninemia/phenylketonuria, to maintain an adequate nutritional status and metabolic control. Full article