European Journal of Nutrition最新文献

Background: Excessive intake of fatty acids is a key factor contributing to metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effects of saturated fatty acids (SFA) and unsaturated fatty acids (UFA) on the development of MASLD are uncertain. Therefore, we conducted two-sample Mendelian randomization studies and animal experiments to explore the effects of SFA, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) on the risk of developing MASLD.

Methods: The genetic summary data of exposures and outcome were retrieved from genome-wide association studies (GWASs) and used for five Mendelian randomization methods. A comprehensive sensitivity analysis was performed to verify the robustness of the results. Mice were subjected to different diets followed by assessment of severity of steatosis based on a histological score and determination of hepatic triglyceride levels to investigate the relationships between SFA, MUFA, PUFA and MASLD.

Results: The Mendelian randomization results showed that MUFA (odds ratio: 1.441, 95% confidence interval: 1.078-1.927, P = 0.014) was causally associated with the incidence of MASLD. SFA and PUFA were not causally associated with the incidence of MASLD. Sensitivity analysis did not identify any significant bias in the results. The animal experiment results showed that a MUFA-enriched diet significantly contributed to the development of hepatic steatosis (P < 0.001).

Conclusion: SFA and PUFA did not have a significant causal effect on MASLD, but MUFA intake is a risk factor for MASLD. A MUFA-enriched diet increased the incidence of macrovesicular steatosis and the hepatic triglyceride levels. Therefore, replacing MUFA intake with a moderate intake of PUFA might help reduce the risk of MASLD.

Purpose: The dietary egg-protein hydrolysate Newtricious (NWT)-03 has previously demonstrated improvements in blood pressure and metabolic profiles. However, the long-term effects on vascular function and cardiometabolic risk markers are unknown.

Methods: Forty-four older (aged 60-75) adults with overweight/obesity experiencing elevated Subjective Cognitive Failures (SCF) were randomized into a 36-week, double-blind, placebo-controlled trial. Participants either consumed 5.7 g of an egg-protein hydrolysate (NWT-03) or maltodextrin placebo. Endothelial function (brachial artery flow-mediated vasodilation [FMD] and carotid artery reactivity [CAR] responses after a cold pressor test), arterial stiffness (carotid-to-femoral pulse wave velocity [PWV_c-f]), retinal microvascular calibers, and cardiometabolic risk markers (insulin sensitivity using a 7-point oral glucose tolerance test, serum lipid profiles, and blood pressure) were evaluated.

Results: FMD observed a non-significant trend towards a 0.3 percentage point (pp) increase in the intervention compared to the placebo group (95% CI: [0.0, 0.7]; p = 0.08), and a significant intervention effect was observed on CAR responses based on a 0.7 pp improvement after a cold pressor test (95% CI: [0.1, 1.3]; p = 0.03). No significant overall changes were observed for arterial stiffness as measured by PWV_c-f. Retinal microvascular calibers and cardiometabolic parameters also did not change.

Conclusion: Long-term supplementation with 5.7 g of the egg-protein hydrolysate NWT-03 for 36 weeks improved vascular endothelial function in older adults with overweight/obesity experiencing elevated SCF, which may benefit cardiovascular disease risk. No overall changes in other vascular function markers, retinal microvascular calibers or cardiometabolic risk markers were observed.

Clinical trial registration: The study was registered at ClinicalTrials.gov in January 2021 as NCT04831203: https://clinicaltrials.gov/study/NCT04831203.

Purpose: Although total dietary protein intake has been associated with bladder cancer (BC) risk, the effect of the origin (plant or animal) and the substitutions remain to be understood. This study aimed to investigate the effect of total dietary protein, animal-based protein, plant-based protein, and their substitutions with each other on the risk of BC using a pooled analysis of 10 cohort studies.

Methods: The study was conducted within the "BLadder cancer Epidemiology and Nutritional Determinants" (BLEND) study, including 10 prospective cohort studies from several European countries, the United Kingdom, and the United States. Individual data from 10 prospective cohorts containing 434,412 participants (overall male/female ratio was almost 3:1) with a total of 4,224,643.8 person-years of follow-up was analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) for BC risk for animal and plant-based protein substitutions of 30gram (g) per day (g/day) were estimated by multivariable adjusted HRs using Cox proportional hazards models.

Results: During 11.4 years of follow-up, among 434,412 participants (73.28% female), 1,440 new cases of BC were identified. After multivariable adjustment, no association was observed between the intake of total, animal-based protein, and plant-based protein and BC risk. Replacement of every 30 g/day of animal-based protein intake by the same amount of plant-based protein intake or vice versa was not associated with the risk of BC.

Conclusion: In conclusion, our study found no association between protein intake-whether from animal or plant sources-and the risk of BC. Substituting animal-based protein with plant-based protein, or the reverse, did not influence BC risk. Future studies are required to provide information on the link between animal- and plant-based proteins and BC risk.

Objective: Previous studies have indicated a potential correlation between cheese intake and risk of various diseases. However, establishing a causal relationship is challenging. To address this, we employed Mendelian randomization (MR) to simulate randomized trial groups and to investigate whether there is a causal link between cheese intake and the risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus.

Methods: We conducted a multivariable MR analysis using individual-level data on GERD and Barrett's esophagus from the published datasets. Univariable and multivariable MR investigations were carried out to explore and substantiate the causal association between genetically predicted cheese intake and esophageal diseases. Additionally, a network MR analysis was executed to identify potential intermediate variables.

Results: Based on the primary causal effects model using MR analyses with the inverse-variance weighted (IVW) method, the genetically predicted that cheese intake demonstrated a protective factor of GERD (OR = 0.356; 95% CI 0.256-0.495; P = 8.22E-10) and Barrett's esophagus (OR = 0.223; 95% CI 0.114-0.437; P = 1.19E-5). These effects remained consistent after adjusting for potential confounders such as tobacco smoking (GERD: OR = 0.440; 95% CI 0.347 - 0.558; P = 1.17E-11; Barrett's esophagus: OR = 0.263; 95% CI 0.160 - 0.432; P = 1.33E-7) and BMI (GERD: OR = 0.515; 95% CI 0.424 - 0.626; P = 2.49E-11; Barrett's esophagus: OR = 0.402; 95% CI 0.243 - 0.664; P = 3.72E-4). Furthermore, the network MR showed that BMI mediated 28.10% and 27.50% of the causal effect of cheese intake on GERD and Barrett's esophagus, respectively, with statistically significant mediation effects.

Conclusion: The multivariable MR analysis conducted in this study revealed a reverse causal relationship between cheese intake and GERD and Barrett's esophagus. Furthermore, BMI was potential mediating factor of the cheese intake effects on GERD and Barrett's esophagus. This finding provides causal evidence for the potential protective role of cheese intake in the prevention of esophageal diseases. The mediating effect of BMI suggests that dietary interventions combined with weight management may help reduce the risk of these diseases.

Background and purpose: Bioavailability studies and observational evidence suggest that heme iron (HI) may have greater impact on iron status indicators compared with non-heme iron (NHI). This systematic review and meta-analysis aimed to review the current evidence on the effect of the administration of HI compared with NHI for improving iron status in non-hospitalized population groups.

Methods: We searched Pubmed, CENTRAL, Scopus, Web of Science, and LILACS from inception to July 2024. There was no language restriction or exclusion based on age or iron status. Only randomized controlled trials comparing HI with NHI were considered. A random-effects meta-analysis was performed to compare the effect of treatments for iron status indicators and total side effects (including gastrointestinal side effects). We measured the certainty of the evidence (CoE) using GRADE assessment.

Results: After screening 3097 articles, 13 studies were included. Most of the interventions used HI in low doses combined with NHI. The meta-analysis showed higher hemoglobin increases in children with anemia or low iron stores receiving HI (MD 1.06 g/dL; 95% CI: 0.34; 1.78; CoE: very low). No statistically significant difference between interventions were found for any iron status indicator in the other population subgroups (CoE: very low). Participants receiving HI had a 38% relative risk reduction of total side effects compared to NHI (RR 0.62; 95% CI 0.40; 0.96; CoE: very low).

Conclusion: The current evidence comparing HI with NHI is very limited, preliminary findings suggest that interventions using HI may result in fewer side effects and may be superior in children with iron deficiency or anemia. However, given the very low certainty of the evidence, these results need further investigation through high-quality clinical trials.

Protocol registration: CRD42023483157.

Purpose: Recently, a significant negative correlation has been found between vitamin D (VD) and metabolic associated fatty liver disease (MAFLD), suggesting a potential beneficial role of VD in preventing of MAFLD, while underscoring the importance of exploring its mechanisms.

Methods: The experiment comprised two parts: male C57BL/6J mice (6 weeks) were fed a high-fat diet (HFD) and intraperitoneally injected with vitamin D₃ (VD₃) (1.68 IU/g/week) for 16 weeks. Meanwhile, palmitic acid (PA)-induced HepG2 cells were treated with 1,25(OH)₂D₃ (10 nM). The general conditions of the mice were evaluated by measuring body weight, liver/body weight, serum biochemical parameters, and inflammation indices. Additionally, injury-associated indices and histopathology were used to assess the severity of liver injury. Furthermore, indicators of ferroptosis, including lipid peroxidation, iron aggregation, and the aberrant expression of related proteins, were determined using Prussian blue staining, ELISA assay, and Western blot.

Results: Long-term VD₃ administration significantly reduced body weight gain and the liver/body weight ratio of HFD-induced MAFLD mice, while also improving serum lipid metabolism dysregulation and enhancing insulin sensitivity. The changes in the expressions of liver injury indices and histological manifestations due to VD₃ treatment indicated that VD₃ may exerts beneficial effects on liver injury through inhibiting inflammatory cell infiltration and vacuolation. Importantly, VD₃ supplementation also inhibited ferroptosis by enhancing the body's antioxidant capacity, reducing local iron aggregation, and modulating the expression levels of ferroptosis-related proteins. These findings were further confirmed in a PA-induced HepG2 steatosis cell model, highlighting the pharmacological effects of VD.

Conclusions: VD shows promise in mitigating HFD -induced liver injury by improving metabolic dysregulation and inhibiting ferroptosis, suggesting therapeutic potential in MAFLD.

Purpose: It has been assumed that magnesium (Mg) status may interact with vitamin D status. We therefore aimed at investigating the association between Mg and vitamin D status in a large cohort of adult individuals with a high prevalence of deficient/insufficient vitamin D and Mg status.

Methods: We used data from the Ludwigshafen Risk and Cardiovascular Health Study (n = 2,286) to analyze differences according to serum Mg status in circulating 25-hydroxyvitamin D [25(OH)D] (primary endpoint), 24,25-dihydroxyvitamin D₃ [24,25(OH)₂D₃], vitamin D metabolite ratio and calcitriol, and odds ratios for deficient or insufficient 25(OH)D (secondary endpoints). We performed unadjusted and risk score (RS) adjusted and matched analyses.

Results: Of the study cohort (average age > 60 years), one third was 25(OH)D deficient (< 12 ng/mL), one third 25(OH)D insufficient (12 to < 20 ng/mL), about 10% Mg deficient (< 0.75 mmol/L) and additional 40% potentially Mg deficient (0.75 to 0.85 mmol/L). In adjusted/matched analyses, 25(OH)D was only non-significantly lower in Mg deficient or insufficient groups versus their respective control group (P > 0.05). Only the RS-adjusted, but not the RS-matched odds ratio of 25(OH)D deficiency was significantly lower for the group with adequate versus deficient/potentially deficient Mg status (0.83; 95%CI: 0.69-0.99), and only the RS-matched, but not the RS-adjusted odds ratio of 25(OH)D insufficiency was significantly lower for non-deficient versus deficient Mg status (0.69; 95%CI: 0.48-0.99). Other adjusted or matched secondary endpoints did not differ significantly between subgroups of Mg status.

Conclusions: Our data indicate only little effect between Mg and vitamin D status in adults with high prevalence of vitamin D deficiency and insufficiency.

Purpose: This study analyzed the relation of energy and macronutrient intake at dinner versus breakfast with the risk of hyperhomocysteinemia (Hhcy).

Methods: Up to 12,474 adults, in which 1,387 with Hhcy, completed a questionnaire about energy and macronutrient intake in the National Health and Nutrition Examination. The differences (Δ) in that between dinner and breakfast (Δ = dinner - breakfast) were categorized into quartiles. Logistic regression analyses or restrictive cubic spline regressions were conducted to determine the relation in Δ and the risk of Hhcy, as well as the change in risk when 5% energy at dinner was substituted with those at breakfast through isocaloric substitution models.

Results: After adjusted the confounders, results showed that compared to the research objects in the lowest quartile, those in the highest quartile were more prone to get Hhcy (odds ratio (OR)_{Δ energy} = 1.26, 95% CI = 1.03-1.56; OR_{Δ protein} = 1.25, 95% CI = 1.01-1.55; OR_{Δ PUFA} = 1.22, 95% CI = 1.01-1.49, respectively). Isocalorically replacing 5% energy at dinner with energy at breakfast was related to 5% lower Hhcy risk. Replacing 5% of energy provided by protein at dinner with that by protein or PUFA at breakfast was related to 10% and 11% lower Hhcy risk, respectively. Replacing 5% energy provided by PUFA at dinner with that by protein or PUFA at breakfast were associated with 8% and 6% lower Hhcy risk, respectively.

Conclusion: The optimal intake period for energy, protein, and polyunsaturated fatty acid intake for reducing Hhcy risk in adults was the morning.

Purpose: Autophagy is a degradation process whose activation underlies beneficial effects of caloric restriction. Isothiocyanates (ITCs) induce autophagy in cancer cells, however, their impact on primary cells remains insufficiently explored, particularly in non-epithelial cells. The aim of this study was to investigate whether ITCs induce autophagy in primary (non-immortalized) mesenchymal cells and if so, to determine the molecular mechanism underlying its activation and consequences on cell functioning.

Methods: Primary human dermal fibroblasts (HDFa) and prostate cancer cells (PC3) as well as two ITCs, sulforaphane and phenethyl isothiocyanate, were applied. Cell viability was measured by the MTT test, protein synthesis - by ³H-leucine incorporation, and protein level - by immunoblotting. A number of mutant huntingtin (mHtt) aggregates was assessed by fluorescence microscopy.

Results: Both ITCs efficiently induced autophagy in fibroblasts which coincided with suppression of mTORC1 - a negative autophagy regulator - and protein synthesis arrest. A dephosphorylation of mTORC1 substrate, S6K1, and ribosomal S6 protein was preceded by activation of AMPK, an inhibitor of mTORC1 and autophagy activator. A similar response was observed in phenethyl isothiocyanate-treated prostate cancer cells. We also showed that ITCs-induced autophagy and/or translation block do not affect cells viability and can protect cells against an accumulation of mHtt aggregates - a main cause of Huntington's disease.

Conclusion: Our study showed that ITCs induce autophagy and inhibit protein synthesis in both primary mesenchymal and cancer cells via modulation of the AMPK-mTORC1-S6K1 pathway. Moreover, it suggests that ITCs might have a potential in developing therapeutics for Huntington's disease.