Search Results (5,483)

Evidence from clinical trials indicates that dietary protein plays an important and often underappreciated role in lipoprotein lipid metabolism. For this narrative review, literature searches were conducted in the PubMed and Cochrane Central Register of Controlled Trials databases for articles describing randomized controlled trials (RCTs) and systematic reviews and meta-analyses of RCTs, as well as dietary guidelines and dyslipidemia management recommendations, using search terms for protein quantity, source (e.g., animal- and plant-based), and type (e.g., dairy, meat, soy, and nuts) and effects on lipids and lipoproteins in humans. Findings indicated that dietary intakes of both animal-based and plant-based proteins, when replacing refined carbohydrates or saturated fatty acids, lower circulating concentrations of atherogenic lipoproteins. Protein from plant sources appears to produce a somewhat larger effect on lipoprotein lipid concentrations than protein from animal sources. Individual amino acids (e.g., branched-chain amino acids), protein food fractions (e.g., whey), and food-derived peptides may independently impact lipoprotein lipid metabolism. Beyond the effect of replacing one macronutrient for another, the biochemical pathways responsible for the effects of dietary protein on lipoprotein lipid metabolism in humans have not been fully defined. The importance of dietary protein in a healthy diet is emphasized in recent dietary recommendations for the general population and for individuals with dyslipidemias. Additional research is warranted to determine the amount of dietary protein and the best balance of food source(s) to optimize its benefits on lipoprotein lipid concentrations, as well as the mechanisms for these effects. Full article

Apolipoprotein A-IV (ApoA-IV) is a glycoprotein secreted by the small intestine to regulate lipid metabolism and satiety. Its role in insulin-independent glucose homeostasis remains largely unknown. In this study, we demonstrate that intestinal ApoA-IV overexpression significantly attenuates diet-induced obesity and hyperglycemia following severe β-cell loss. Over a 20-week high-fat diet challenge, ApoA-IV transgenic (ApoA-IV-Tg) mice maintained significantly lower adiposity than wild-type controls, driven by elevated energy expenditure and fatty acid oxidation rather than reduced caloric intake. Beyond weight maintenance, ApoA-IV maintained excellent systemic glycemic control and enhanced peripheral insulin sensitivity. Most notably, ApoA-IV significantly attenuated hyperglycemia following streptozotocin (STZ)-induced β-cell ablation, maintaining glucose stability despite severe insulin deficiency. Mechanistically, this protection results from a blunted glucagon response and the subsequent suppression of the hepatic pCREB-G6Pase gluconeogenic signaling pathway. In vitro evidence confirms that ApoA-IV directly inhibits pancreatic α-cell glucagon secretion through an LDL receptor-related protein 1 (LRP1)-dependent pathway, reinforced by the precise co-localization of LRP1 and glucagon in pancreatic islets. Furthermore, ApoA-IV-Tg mice were protected from the STZ-induced corticosterone surge and systemic lipolysis. Collectively, these findings establish the ApoA-IV–LRP1 signaling axis as a potent metabolic switch, providing a promising insulin-independent strategy for managing obesity and diabetes. Full article

Background/Objectives: This study describes body composition, bone mineral density (BMD), and dietary intake in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation compared to healthy children. Methods: In this prospective observational study, dual-energy X-ray absorptiometry was used to assess appendicular lean mass index (ALMI), fat mass index (FMI), fat mass percentage (FM%), and BMD, and a 4-day dietary record was used to assess dietary intake at 3 months and 1 year post-transplant. Healthy children were assessed once by the same methods. Results: We included 28 patients (mean 10.3 years, SD 4.0) and 50 healthy children (mean 10.0 years, SD 3.6). At 1 year, median Z-scores were lower for ALMI (−1.34 vs. 0.40, p < 0.001), higher for FMI (0.34 vs. −0.33, p < 0.012) and FM% (0.59 vs. −0.98, p < 0.001), lower for BMD total body less head (−1.0 vs. 0.3, p = 0.006), but similar for BMD spine compared to healthy children. At 1 year, 9/15 (60%) had ALMI Z-score ≤ −1, 6/15 (40%) had FMI Z-score ≥ 1, 5/15 (33%) had FM% Z-score ≥ 1, and 8/18 (53%) had BMD total body less head Z-score ≤ −1, and 3/15 (20%) had BMD spine Z-score ≤ −1. Dietary intake improved, and at 1 year, energy and protein intakes were comparable, fat, calcium, and vitamin D intakes were higher, but fiber intake remained lower in patients than in healthy children. Conclusions: Patients had a more unfavorable body composition and bone health. Dietary intake improved from 3 months to 1 year post-transplant. However, the results indicate a need for nutritional follow-up, particularly targeting protein, fat, fiber, calcium, and vitamin D. Full article

Visceral organ mass is a major determinant of maintenance energy requirements in cattle, suggesting that equations to predict visceral organ mass could increase the accuracy of estimates of energy requirements. The objective of this meta-analysis was to quantify the relationships of visceral organ mass with the chemical composition of the diet, as well as animal and management characteristics. A database of 170 treatment means from 38 studies was assembled from published literature. Mixed-effects models with animal, management, and diet characteristics as fixed effects and study as a random effect were selected based on the lowest corrected Akaike information criterion (AICc) and evaluated via leave-one-trial-out cross-validation. Out of 16 organs, 15 had concordance correlation coefficient (CCC) values over 0.900, and cross-validated coefficient of determination (R²) values ranged from 0.728 to 0.967 across organs. Dry-matter intake, days on feed, and fiber-related diet characteristics (roughage level, neutral detergent fiber, and physically effective neutral detergent fiber) were the most consistently retained predictors, with crude protein and metabolizable energy concentrations being retained less frequently. These equations provide a quantitative basis for more accurate estimation of visceral organ mass in cattle. Full article

The growing aging population is a primary driver of chronic, long-term health conditions. The rising prevalence of cognitive decline in older populations is a pressing public health issue due to its impact on health and social care and its emotional toll on family members. A lesser-known condition is sarcopenia—the age-related debilitating loss of skeletal muscle mass and function which leads to weakness and loss of mobility, quality of life and social independence. Neither health condition has a clear pharmacological treatment pathway. Diet and nutrition have therefore received the most attention for disease prevention. This review evaluates the research on the association between sarcopenia and cognitive decline and how both conditions may be linked to protein intake. While findings can be inconclusive or contradictory, a higher consumption of protein may protect against declines in physical and cognitive health, either acting separately or synergistically with exercise. The evidence supports the recommendation for a daily intake of protein higher than the current guideline of 0.8 g/kg/d for older people. Evidence suggests that healthy dietary patterns such as the Mediterranean diet appear to positively influence cognitive health in older people. Furthermore, the impact of specific high-protein foods, including egg, soy and dairy foods, on cognitive health has been reviewed, again with a suggestion that their consumption may mitigate against cognitive decline. Functional foods aimed at the aging population who wish to increase their protein intake and avert or delay the onset of these health conditions could play an important role in preventive nutrition, especially if they are formulated around the protein-rich foods which appear to positively impact cognitive health. Full article

New Zealand working farm dogs can struggle to maintain their body weight and condition during periods of high workload, despite substantial energy intake, highlighting the need to optimise energy balance. One potential strategy for reducing overall energy demands is to reduce energy expenditure for thermoregulation, particularly during colder conditions, which may improve both recovery and energy utilisation. This study investigated whether wearing coats influenced the sleep behaviour, activity, and apparent nutrient digestibility of outdoor-kennelled dogs. Eight adult working-breed dogs (n = 8) were studied using a randomised cross-over design, in which dogs wore a coat or no coat during overnight periods (15:00–09:00 h). Behaviour was monitored using triaxial accelerometers and classified using a validated machine learning model, while apparent nutrient digestibility was determined from pooled faecal samples. Dogs spent more time sleeping when wearing a coat compared to no coat (48.1% vs. 40.0%, p = 0.008), with the effect being most evident during cooler evening hours. Time spent resting and being active was reduced when coats were worn (p < 0.05), while overall activity did not differ (p = 0.856). No differences were observed in apparent digestibility of energy or nutrients (p > 0.05), although protein digestibility tended to be higher when coats were worn (p = 0.079). These findings suggest that coats can improve sleep behaviour, likely through improved thermal comfort. While this study was conducted in research dogs under relatively mild temperature conditions, the results indicate the potential welfare and functional benefits for working farm dogs. Full article

Lead (Pb) exposure induces liver injury through oxidative stress, inflammation, and gut–liver axis disruption. This study evaluated the protective effects and associated mechanisms of fucoidan (FU) against Pb-induced liver injury in mice. C57BL/6 mice were exposed to lead acetate and treated with FU. High-dose FU (FU-H) improved food intake, body weight, and liver index; decreased Pb levels in serum and liver; and increased fecal Pb content. Compared with the Model group, FU-H reduced serum ALT, AST, and ALP by 54.8%, 38.6%, and 21.7%, respectively. FU-H restored hepatic SOD and GSH by 10.9% and 46.5% and decreased hepatic MDA by 45.9%; it also restored serum SOD and GSH by 30.4% and 24.0%, decreased serum MDA by 19.6%, and suppressed TNF-α, IL-6, and IL-1β by 15.7%, 21.1%, and 14.9%, respectively. Integrated RNA sequencing and network toxicology suggested that insulin-like growth factor-binding protein 1 (IGFBP1) may be associated with FU-mediated protection, and recombinant IGFBP1 partly weakened FU-associated hepatoprotection. Moreover, 16S rRNA sequencing and untargeted metabolomics showed that FU reshaped Pb-disrupted gut microbiota and altered fecal tryptophan metabolism. Exogenous tryptophol supplementation partially alleviated Pb-induced liver injury. Overall, FU protection was associated with reduced Pb burden, IGFBP1-related redox modulation, and gut microbiota-derived tryptophol metabolism. Full article

Background/Objectives: In phenylketonuria (PKU), high blood phenylalanine (Phe) levels during pregnancy negatively influence foetal organogenesis and growth, leading to maternal PKU syndrome. Pregnancies must be carefully planned in order to maintain blood Phe levels ≤ 360 µmol/L pre-conception and throughout pregnancy. Our aim was to study metabolic control in PKU pregnancies across Europe. Methods: Eleven centres managing PKU participated. Data on blood Phe levels (µmol/L), natural protein intake (g/day), protein substitute intake (g/day) and maternal weight (kg) during pregnancy were collected retrospectively from dietetic records between 2012 and 2018. Results: In total, 84 female patients with PKU, accounting for 102 pregnancies (mean age: 30.4 ± 4.8 years), participated. Of these, 7 had hyperphenylalaninemia (HPA), 26 had mild PKU, 55 had classical PKU and 14 were unclassified. Sapropterin was prescribed in two pregnancies. Only 27% (28/102) of pregnancies successfully achieved consistent blood Phe levels ≤ 360 µmol/L for at least 2 weeks pre-conception. During pregnancy, 88% of blood Phe levels were ≤360 µmol/L, with a mean Phe of 229 ± 65 µmol/L. The mean number of blood Phe samples was 60 (1.5 per week) per pregnancy. In pre-pregnancy, over a mean of 2.9 years, only 35% of blood Phe levels were ≤360 µmol/L and 61% were <600 µmol/L. Post-pregnancy, over a mean of 2.8 years, 43% of Phe levels were <600 µmol/L with mean Phe 462 ± 226 µmol/L and 724 ± 230 µmol/L, respectively. 25% (25/102) had no levels performed post-pregnancy (mean of 2.8 ± 1.6 years) compared to 7% (7/102) pre-pregnancy (mean of 2.9 ± 1.5 years). Mean prescribed Phe intake pre-/during/post-pregnancy was 810 ± 721 vs. 787 ± 552 vs. 1110 ± 722 mg/day. Natural protein intake was 17 ± 15 vs. 17 ± 11 vs. 23 ± 15 g/day. Protein equivalent from protein substitute intake was 57 ± 21 vs. 66 ± 16 vs. 50 ± 23 g/day and total protein remained stable, 73 ± 14 vs. 83 ± 14 vs. 71 ± 19 g/day (1.1 ± 0.3 vs. 1.1 ± 0.4 vs. 1.0 ± 0.4 g/kg/day). Conclusions: Although a high level of metabolic control was maintained during pregnancy, fewer than 30% of pregnancies achieved constant Phe levels ≤ 360 µmol/L prior to conception, with minimal monitoring post-pregnancy. The long-term impact on the offspring remains unknown and requires further investigation. Full article

Background/Objectives: Diabetic neuropathy is a prevalent complication of type 2 diabetes mellitus (T2DM), but the contribution of dietary factors to neuropathy severity remains insufficiently characterized. This study investigated associations between dietary patterns, nutrient intake, and neuropathy severity in 300 adults with T2DM from Northeastern Romania. Methods: Dietary intake was assessed using a validated food frequency questionnaire, and five dietary patterns were derived using principal component analysis. Neuropathy severity was analyzed as an ordinal outcome using logistic regression models adjusted for age, sex, HbA1c, diabetes duration, and treatment. Results: Higher adherence to Western/fast-food and alcohol and animal fat dietary patterns was associated with greater neuropathy severity in unadjusted analyses, whereas a healthy/prudent pattern showed inverse associations; however, these relationships were attenuated after multivariable adjustment. In contrast, higher intakes of protein (OR = 0.98, 95% CI: 0.97–0.99), magnesium (OR = 0.99, 95% CI: 0.98–1.00), zinc (OR = 0.80, 95% CI: 0.69–0.94), vitamin B3 (OR = 0.94, 95% CI: 0.89–0.99), and vitamin B12 (OR = 0.76, 95% CI: 0.62–0.93) remained independently associated with lower neuropathy severity after adjustment. Conclusions: These findings suggest that specific nutrient intakes may be more strongly associated with diabetic neuropathy severity than overall dietary patterns, highlighting potential nutritional targets for neuropathy risk reduction and clinical management in patients with T2DM. Full article

Underweight in pregnant women adversely affects the next generation. Although young female underweight has become an important issue even in developed countries, the precise mechanisms that induce an underweight status in young women remains unknown. To examine the influence of feeding timing in young women on the following underweight conditions, we examined the effects of chronic light–dark cycle-reversed feeding restriction on post-restriction dietary behaviors using adult and young adult female rats. Eight- and 24-week-aged female Wistar rats were classified into three groups: (1) the control group (without time or calorie restriction), (2) the night-time-fed group that was fed only during the active phase, and (3) the daytime-fed group that was fed only during the non-active phase. After a 4-week feeding restriction, all groups were additionally fed ad libitum for 7 weeks with daily food intake and weight gain measurements. After sacrifice, mRNA expressions of neuropeptide Y (NPY), agouti-related protein (AgRP), orexin-A, pro-opiomelanocortin (POMC), and thyrotropin-releasing hormone (TRH) in the hypothalamus and leptin in the fatty tissues were examined by real-time PCR. Daytime-fed groups decreased food intake during restriction. After stress relief, adult rats showed a rebound increase in food intake beyond the level of the control group, whereas young adult rats showed no significant rebound response. At the end of the non-restricted period, both adult and young adult rats in the daytime-fed group reduced NPY expression in the hypothalamus. These findings indicate that recovery responses in food intake against chronic light–dark cycle-reversed stress are different between adult and young adult rats. The lower response in young adult rats may provide clues to elucidating a new mechanism for underweight status in young females. Full article

Background: Shifting toward more plant-based diets is promoted for health, environmental, and ethical reasons. However, the nutritional consequences of reducing animal-based foods, particularly across age groups with specific dietary needs, remain insufficiently understood. Methods: In this simulation study, we used dietary intake data from 3570 participants in the Dutch National Food Consumption Survey (2019–2021) to evaluate how replacing animal-based foods with plant-based alternatives affects the intake of protein, essential amino acids (EAAs), vitamins, and minerals across different age groups. Two substitution scenarios were modeled: a nutritionally conscious and a less conscious plant-based dietary pattern. Results: Total protein intake decreased in both scenarios, with the strongest reductions observed in elderly individuals (71–79 years). Vitamin intake, particularly B vitamins and vitamin A, declined in most age groups, and vitamin D remained chronically low. Mineral intake also decreased, notably for calcium, iron, iodine, selenium, and zinc, especially among women and adolescents. Conclusions: These results underscore the importance of dietary planning and targeted fortification when promoting plant-based eating patterns. Future research should refine bioavailability estimates and evaluate the long-term health effects of such dietary transitions across life stages. Full article

Background: Cancer-related cachexia is primarily characterized by systemic inflammation and progressive muscle wasting, which is why a high-protein diet (from 1.2 to 1.5 g/kg/day) is commonly recommended. However, concerns remain that an excessive supply of amino acids could promote tumor growth due to the metabolic flexibility of cancer cells, thereby favoring proliferation and survival. Systematic evidence addressing these concerns under controlled conditions for various types of cancer cells remains limited and inconclusive. Methods: We investigated the short-term effects of all 20 amino acids at both moderate (2×) and high (10×) concentrations to evaluate three key oncological endpoints in four human cancer cell lines: MDA-MB-231 (breast), HT29 (colorectal), PC3 (prostate), and PANC-1 (pancreatic). Cell proliferation was assessed by BrdU incorporation, metabolic activity by WST-1 assay, and apoptosis signaling by caspase-3/7 activity measurement. Results: Amino acid supplementation was not associated with a significant change in proliferation at either concentration across all four cell lines studied. Metabolic activity showed only minor variations throughout, with PC3 cells exhibiting slightly greater variability, although this did not reach statistical significance. Caspase-3/7 activity remained largely unchanged under all conditions; however, high-concentration lysine induced an approximately 2.5-fold increase in PANC1 cells, which was not statistically significant. Conclusions: These findings suggest that short-term exposure to individual amino acids, even at supraphysiological conditions, does not acutely enhance proliferative activity in the cancer cell lines studied, supporting the rationale for adequate protein and amino acid intake in patients with cancer cachexia. Full article

Background: Branched-chain amino acids (BCAAs) regulate muscle protein metabolism, yet the systematic characterization of their dose-dependent morphological effects on exercised skeletal muscle remains limited. This study investigated the dose–response relationship between BCAA supplementation and skeletal muscle adaptations in exercise-trained mice. Methods: Seventy male Kunming mice were randomly assigned to seven groups (n = 10): a background group (no exercise), a control group (exercise + saline), and five exercise groups receiving BCAAs at 1–5 g/kg/day via intragastric gavage. Mice in the exercise groups performed 45 min of swimming daily (6 days/week) for 50 days. Gastrocnemius muscles were processed using hematoxylin–eosin staining, Masson trichrome staining, Gomori aldehyde fuchsin staining, and transmission electron microscopy. Data were analyzed using one-way ANOVA with Dunnett’s post hoc test. Results: BCAA supplementation increased gastrocnemius wet weight-to-body weight ratios and promoted denser fiber packing in a dose-dependent manner up to 3–4 g/kg/day. Deep-staining fiber proportion (putatively type II-like) increased progressively with BCAA concentration, plateauing at doses ≥ 3 g/kg/day, while elastic fiber content continued to rise through 5 g/kg/day. Mitochondrial size decreased as mitochondrial number increased; membrane and cristae thickness peaked at 3 g/kg/day. Sarcomere length, myofibril diameter, sarcoplasmic reticulum size, and transverse tubule diameter exhibited increasing trends. Conclusions: These findings establish a parameter-specific dose–response framework for BCAA-induced muscle remodeling. A supplemental dose of 3 g/kg/day above background dietary intake represents an effective threshold for maximizing indices of hypertrophic gains and mitochondrial structural maturation potentially indicative of functional enhancement. Higher doses (≥4 g/kg/day) elicited additional benefits in fiber density, mitochondrial proliferation, and elastic fiber content. Supplemental BCAA dosing strategies above constant background intake should be tailored to target specific structural outcomes, with functional validation required to confirm physiological relevance. Full article

This study assessed the effect of dietary supplementation with Kluyveromyces lactis (K. lactis) hydrolysate (HKL) on growth performance, apparent nutrient digestibility, systemic immune–antioxidant status, and fecal microbiota in weaned piglets. A total of fifty-four piglets, with an initial body weight of 6.07 ± 0.086 kg and age of 25 ± 1 days, were randomly assigned to three dietary treatments over 28 days (6 replicates per treatment; 3 piglets per replicate): a control diet (CON), CON supplemented with 5 g/kg HKL (HKL1), or CON supplemented with 10 g/kg HKL (HKL2). Throughout the trial, growth performance was monitored, apparent total tract digestibility of nutrients was determined, serum samples were collected for immune and antioxidant assessments, and fecal samples were gathered for microbiota analysis. The results indicated that compared to the CON group, both HKL1 and HKL2 groups exhibited improved growth performance, as evidenced by increased average daily feed intake (ADFI) from day 0 to 28 (p < 0.05). Furthermore, HKL2 significantly enhanced average daily gain (ADG) from day 0 to 14 and reduced the feed-to-gain ratio (F: G) during the same period (p < 0.05). Diarrhea incidence was markedly decreased by HKL supplementation at both day 1–14 and day 15–28 (p < 0.001). HKL supplementation increased the apparent digestibility of dry matter, ash, calcium, and phosphorus (p < 0.05). On day 14, serum total protein and immunoglobulin A (IgA) levels were elevated, while malondialdehyde (MDA) levels were reduced in HKL-supplemented piglets (p < 0.05). By day 28, serum immunoglobulin G (IgG) concentrations, as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, were increased, while interleukin-6 (IL-6) levels were decreased in HKL-supplemented piglets (p < 0.05), suggesting HKL possesses immunomodulatory and antioxidant regulatory capacities. HKL also enriched several health-associated commensal bacteria, including [Eubacterium]_xylanophilum_group, unclassified_f_Peptostreptococcaceae, Candidatus Saccharimonas, Erysipelotrichaceae_UCG-003, and Negativibacillus, suggesting a microbiota-modulatory effect in weaned piglets. These results indicate that dietary supplementation with HKL could improve growth performance and nutrient utilization, reduce post-weaning diarrhea, and promote a more favorable immune–antioxidant status and microbial profile in weaned piglets, with the 10 g/kg dosage demonstrating greater overall efficacy. These findings provide a theoretical basis for the development of novel K. lactis products and the application of K. lactis hydrolysate in weaned piglets. Full article

Nitrogen use efficiency (NUE) is commonly calculated as the ratio of milk nitrogen output to nitrogen intake in dairy cows. However, because milk nitrogen output is intrinsically determined by milk production and nitrogen intake is largely driven by dry matter intake, conventional NUE is mathematically dependent on production level and feed intake. This dependency makes it difficult to distinguish apparent efficiency caused by higher milk yield from intrinsic biological efficiency in nitrogen utilization. Therefore, this study aimed to evaluate NUE in dairy cows using a combined mathematical and metabolic framework based on residual NUE (rNUE) analysis. A total of 126 early-lactation Chinese Holstein cows were screened, and 16 high-NUE and 16 low-NUE cows were selected after matching for parity, days in milk, and dry matter intake. High-NUE cows had greater milk yield, milk nitrogen output, and NUE than low-NUE cows, despite similar nitrogen intake. They also exhibited higher ruminal microbial crude protein and ammonia nitrogen concentrations, a lower acetate-to-propionate ratio, and reduced circulating essential and total amino acid concentrations. Multiple regression analysis showed that energy-corrected milk and dry matter intake explained 71.4% of the variation in NUE. The residuals from this model were defined as rNUE, which was independent of milk production. After removing production-related effects, rNUE remained positively associated with ruminal microbial crude protein and ammonia nitrogen concentrations, and negatively associated with the acetate-to-propionate ratio and circulating amino acid pools. These findings indicate that conventional NUE in dairy cows is largely driven by production level, whereas residual-based modeling can identify a production-independent component associated with rumen nitrogen metabolism and amino acid utilization. The residual NUE approach provides a useful mathematical and metabolic framework for evaluating intrinsic NUE in dairy cows beyond milk production level. Full article